本文へスキップ

IRIG pursuits further potential of egg.

Japanese

Publications

List of our scientific papers on IgY is shown below.
Japanese titles mean that the original paper is published and available only in Japanese. However some have been translated by our staff and made available in English.




<Pet care>


歯周病罹患猫におけるグロビゲンPG(卵黄リベチン)の歯周病改善効果 ()

Periodontal disease improving effect of Globigen PG (yolk livetin) in cats with periodontal disease.

Companion Animal Practice, 2016, 323; 88-93

中西信夫ら:京都動物検査センター

近年,優れたベットフードの開発や,ワクチン接種による感染症の予防や治療技術の向上により犬・猫の平均寿命が延びている反面,高齢に伴う腫瘍疾患,循探器疾患の罹患率の上昇は避けられない。また,犬・猫は,歯のケアがされにくく4歳齢以上では80%以上が口腔内のトラプルを抱えている。ロ腔疾患の中でも, 特に歯周病は注意しなければならない。犬・猫の歯周病の初期症状はヒトと同様に,歯の根元の炎症による赤みや腫脹などの歯肉炎で口臭(腐敗臭)が強くなる。さらに進行すると軽い刺激で歯茎から出血し,歯肉が歯を支えられなくなり歯がグラグラと動くようになる。歯根膜や歯槽骨などの歯周組織に炎症が達すると痛みによって,摂食などの日常生活に影響を及ぽすだけでなく,心臓,腎臓,肝臓などの循環器や代謝器への疾患および免疫力低下にも影響する。歯周病予防は歯垢を蓄積しないよう,歯垢の除去が基本である。犬においては多くの啓蒙活動により歯周病対策が普及して飼い主の認知が向上し市場にも対策用品が多く販売されているため,飼い主による歯みがきや,例として歯みがきガムのおやつなどによる予防法が日常化しつつある。しかし猫においては,犬ほど飼い主の歯周病に対する意識や対策用品が普及していないのが現実である。また,猫では飼い主による歯みがきは犬以上に難しいため, 歯垢除去の機会が少なく歯周病が進行しやすい。実際アニコム損害保険(株)「どうぶつ健保」の統計において,猫の手術の諸求件数の全体の2割が歯周病、口内炎を治療する目的の手術であり手術別の順位が1位と報告されている(2位は腫瘍、3位が消化管内異物とつづく)。現状の歯周病治根は, ヒトと同様でスケーリング・ルートプレーニングによって機械的にプラークと歯石を除去した後、抗菌薬の投与を行うのが一般的である。これは麻酔下での治療となるため加齢に伴って大きな負担となる。しかし,猫の歯周病は,完治が難しく寿命に大きくかかわることから、 犬と同様に啓蒙活動と歯周病対策用品の普及などの取り組みがこれまで以上に必要である。(株)イーダブルニュートリション・ジャパンは,ニワトリに歯周病菌が産生する病原因子を接種することで,病原因子に対する特異抗体を卵黄に産生させる技術を開発し,その抗体による歯周病予防効果を実証してきた。また,本誌においても特異抗体を含有する卵黄を配合した犬用ドライフ ード給与による歯周病罹患犬における改普効果が紹介されている。今回我々は歯周病罹患猫を対象とした評価試験を実施したのでその結果を紹介する。

 

 

歯周病罹患犬に対する卵黄リベチン(Immunoglobulin Yolk:IgY)を利用した経口受動免疫 ()

Oral passive immunity using egg yolk ribetin (Immunoglobulin Yolk: IgY) for dogs with periodontal disease.

Companion Animal Practice, 2013, 286; 75-81

児玉義勝ら

特巽的IgYの作成は鳥類に備わっている「卵黄内への輸送機能」の生物学的な仕組みを利用する。目的とするターゲット抗原を親鶏に接種することで,血消中に接種抗原に対する免疫グロプリンが産生され,それを卵黄に蓄積して産卵する。親鶏に接種する抗原の種類を変えるだけで,特異性の異なるいろいろなIgYが生産できる。リベチンとは,卵黄たんばく質に約30%含まれる水溶性たんぱく質のことであり「α-リベチン」「β-リベチン」および「γ-リベチン」の3種類が区分されている。それぞれの構成比は235であることが報告されている。α-リベチンは親

鳥の血清アルプミン,β-リベチンは血清α2-グルコプロテインである。Y-リベチンは血清y-グロプリンが卵黄内輸送機能によって卵黄に移行したものである。このIgYは,哺乳類のIgGに相当するものであるが,分子サイズは大きく180kDである。H鎖不変領域が4個のドメインからな

り,H鎖に関しては哺乳類IgGと異なる。近年,優れたペットフードが開発されたことにより犬・猫の寿命が伸び,それに伴って歯周病罹患字が増大している。歯周病は口腔バイオフィルム感染症で,その主要起因菌としてPorphyromonas gingivalisPorphyromonas gulaeが注目されている。本菌最大の病原因子は菌体外膜に局在しているシステインプロテアーゼから成るジンジパイン(gingipain) であることが明らかにされている。現状の歯周病治療はヒトと同様で,スケーリング・ルートプレーニングによって機械的にプラークと歯石を除去した後,抗生物質の投与を行うことが一般的である。これは麻酔下での治療となるため,加齢に伴って動物に大きな負担となる。このような状況を解決するため,プラークコントロールを目的としたペレットフードなどの開発が国内外で行われてきたが,満足できる結果は得られなかった。著者らは,これまでに本ジンジパインを標的にした経口受動免疫の確立を目指して精力的な研究を実施してきた。本稿では,P.gingivalisならびにP.gulaeの最大の病原因子であるジンジパインの多様な病原性機能,ジンジパインに対するIgYin vitroならびに歯周病罹患犬を対象にしたin vivo試験の結果を紹介したい。

 

 

Effect of passive immunization by anti-gingipain IgY on periodontal health of dogs

歯周病罹患犬における抗ジンジパインIgYによる受動免疫効果

Veterinary Science Development, 2011, 1(e8); 35-39

Rahman A.K.M. Shofiqur, et al.

http://www.pagepress.org/journals/index.php/vsd/issue/view/169

http://www.pagepress.org/journals/index.php/vsd/article/view/vsd.2011.e8/pdf

Anti-gingipain IgY (IgY-GP), known as hyperimmune γ-livetin from egg yolk, inhibits the enzyme activity, growth and adherence of Porphyromonas gingivalis to gingival epithelial cells. Our objective was to evaluate the efficacy of IgY-GP on periodontal health of dogs. IgY-GP was prepared from the egg yolk of hens immunized with the gingipain from Porphyromonas gingivalis ATCC 33277. Two in vivo trial models were conducted on 15 adult dogs with periodontitis by giving IgY-GP-supplemented dog feed for 8 weeks and direct application of the IgY in dental ointment to the periodontal pockets at weekly interval for 4 weeks. Clinical parameters including gingivitis, periodontitis, oral health index, bleeding on probe (BOP), pocket depth (PD), and dental calculus removal pattern for selected premolar teeth were recorded at baseline, 4 and 8 weeks post treatment. IgY-GP showed strong cross-reactivity with gingipain from Porphyromonas gulae and inhibited the enzyme activity in vitro. In the dog trials, IgY-GP resulted in significant improvement of oral health parameters including gingivitis and periodontitis scores, BOP, dental calculus removal. No adverse events during and after antibody applications were noted. Oral immunotherapy by using IgY-GP is a new promising alternative to conventional preventive and therapeutic methods to improve oral health status in dogs.

 

 

卵黄抗体IgYを含むサプリメントを用いた口腔内清浄化の試み(和)

An attempt to clean the oral cavity using a supplement containing the egg yolk antibody IgY.

infoVets, 2010, 145(5); 43-45

栗田典子ら:栗田どうぶつ病院

口腔から肛門にいたる消化器は、体に必要なマテリアルを摂取し、不要物を排泄する生体維持の根幹をなす臓器である。口腔は、物を取り込み咀嚼し嚥下する第一の窓口であり、局所の健全をはかることは体全体の健康をはかることにもなる。近年、口腔環境の悪化が消化器のみならす、代謝器や循環器の疾患にもなんらかの関わりがあるという報告がある。ほとんど歯のケアをされないペットは、歯周病の罹患率が高く80%に及ぶという報告もみられている(Harvey, 1993)。ペットの歯周病については多くの情報が出されており、飼い主の意識にも対策の重要性が認知されてきているように思われる。対策としては、歯垢除去のための歯磨きが最良の予防手段であるが、ペットが嫌がる、手間がかかるなど思うように任せない情況もあり、歯磨きガムなども果たしてどこまで効果があるか不明である。獣医臨床の現場においても、ペットの口腔内環境を整備する安全で効果的な方法が望まれている。良い素材を日常的、予防的に使用することによって歯周病にかかわる多くのリスクを回避できればQOLを上げ、さらに安定した寿命を終えることが可能になるだろう。そのような視点に立ち、口腔内清浄化を意図したサプリメントを入手し、有用性の検討を行ったので報告する。

 

 

Passive protection of dogs against clinical disease due to Canine parvovirus-2 by specific antibody from chicken egg yolk

鶏卵抗体を用いたイヌパルボウイルス-2による臨床症状に対する受動防御

The Canadian Journal of Veterinary Research 2006, 70 : 62-64

Sa Van Nguyen, et al.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1325096/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1325096/pdf/cjvr70pg062.pdf

The protective effect of immunoglobulins derived from chicken egg yolk (IgY) against infection by Canine parvovirus 2 (CPV-2) was evaluated in 10 beagle dogs orally challenged with a strain of the virus. The 2-mo-old dogs were divided into 3 groups and treated with powders containing CPV-2 IgY or normal egg yolk for 7 d after the challenge. The 4 dogs receiving normal egg yolk (control group) demonstrated mild symptoms typical of CPV-2 infection, such as vomiting, diarrhea, and weight loss. No symptoms were observed by 16 d after challenge in the 3 dogs receiving 2 g of IgY powder. Of the 3 dogs receiving 0.5 g of IgY powder, 2 had clinical CPV-2 disease; however, the manifestations were less severe than in the control group. Furthermore, the IgY-treated groups had significantly greater weight gain and shorter duration of virus shedding than the control group. These results indicate that IgY is useful in protecting dogs from CPV-2-induced clinical disease.

 

 

Prevention of Human Rotavirus Infection with Chicken Egg Yolk Immunoglobulins Containing Rotavirus Antibody in Cat

抗ロタウイスル鶏卵黄抗体のヒトロタウイルス感染ネコにおける予防効果

Japanese Association for Infectious Diseases, 1990, 64; 118-123

Chikane HIRAGA, et al.: Department of Bacteriology, Saitama Medical School

https://www.jstage.jst.go.jp/article/kansenshogakuzasshi1970/64/1/64_1_118/_pdf

A study was made on the passive protection against rotavirus-induced diarrhea. Chickens were immunized with bovine rotavirus (serotype 1) and the egg yolk immunoglobulins containing a high titer anti-rotavirus neutralizing antibody (CEYI) was obtained. The CEYI was then orally administered to specific-pathogen-free cats, and the cats were infected with human rotavirus. The cats treated with the CEYI remained clinically healthy after challenge, whereas diarrhea occurred in the pracebo-fed cats as control. Virus antigens were detected in feces in all the diarrheal cases in the placebo-fed cats but were only sporadically detected in the CEYI-fed cats. However, the cats were only protected against rotavirus infection by the presence in the gut at the time of inaction of the antibody. These results suggested that continuous administration of the CEYI is capable of preventing children from diarrhea induced by human rotavirus infection and viral shedding.


 



<oral care>


Near Infrared Photo-Antimicrobial Targeting Therapy for Candida albicans

カンジダ・アルビカンスの近赤外線抗菌ターゲット療法

Advanced Therapeutics. January 4, 2021. DOI: 10.1002/adtp.20200221

Hirotoshi Yasui, et al.: Respiratory Medicine, Nagoya University Graduate School of Medicine

https://doi.org/10.1002/adtp.202000221

Near Infraed Photo-Antimicrobial Targeting Therapy for Candida albicans.pdfへのリンク

Drug-resistant microorganisms are a pressing issue, and innovative antimicrobial therapies are required; antibodies targeting antigens on pathogen surfaces have emerged as one such modality. IgY, abundant in chicken egg yolk, confers passive immunity, and is effective against various pathogens; however, its antimicrobial effects remain limited. Near-infrared photoimmunotherapy (NIR-PIT), originally developed as a cancer treatment, specifically kills cancer cells via a photosensitizing phthalocyanine dye (IRDye700Dx; IR700)-conjugated monoclonal antibody, and irradiating NIR light. IgY-photo-antimicrobial targeting therapy (IgY-PAT2), exploiting NIR-PIT, is investigated to destroy only microorganisms. IR700 is conjugated with anti-Candida albicans IgY (CA-IgY) to generate CA-IgY-IR700, which specifically binds various Candida spp. (and not human skin cells). The antimicrobial effect of CA-IgY-PAT2 is dependent on the NIR-light dose (p < 0.0001). CA-IgY-PAT2 significantly reduces the area of ulcers in a mouse model of CA-infected cutaneous ulcers (p < 0.0001), indicating that CA-IgY-PAT2 is a new promising therapeutic method for CA infection.

 

 

Evaluation of lozenges containing egg yolk antibody against Porphyromonas gingivalis gingipains as an adjunct to conventional nonsurgical therapy in periodontitis patients: A randomized controlled clinical trial.

歯周病患者において一般的な手術を行わない治療の補助材としてPorphyromonas gingivalis gingipains に対する卵黄抗体を含んでいる薬用ドロップの評価:臨床試験

Journal of Periodontology, 25 July 2018:

Nguyen SV, et al.

https://doi.org/10.1002/JPER.18-0037

In a previous pilot study, one-time application of anti-Porphyromonas gingivalis gingipain egg yolk immunoglobulin (IgY) into scaling and root planning (SRP)-treated periodontal pockets showed profound improvement of clinical and bacteriological parameters in patients with chronic periodontitis. The present study aims to evaluate the efficacy of daily use of lozenges fortified with the antibody as an adjunct to non-surgical therapy in patients with periodontitis. Sixty-four patients with periodontitis were divided randomly into a test and a placebo group. The groups were treated by SRP followed by a daily use of lozenges containing either specific IgY against P.gingivalis gingipains (test) or a sham-immune IgY (placebo). Gingival bleeding index (GBI), probing pocket depth (PD) and quantitation of P.gingivalis in the gingival pockets were assessed at baseline and 8 weeks after the initiation of treatment and compared by using Wilcoxon signed rank test, Mann-Whitney U-test or t test. Both groups showed significant improvement of all parameters at 8 weeks post treatment (P < 0.001). There was a significant difference in reduction of GBI (P < 0.001) and P.gingivalis cell counts (P < 0.05) in the test group compared with the placebo group. The reduction of PD was greater in the test group compared with the placebo group although there was no statistically significant difference between the two groups. The adjunctive use of lozenges containing IgY antibody against gingipains from P.gingivalis resulted in clinical and microbiological benefits in the treatment for chronic periodontitis. Additional investigations are needed to examine if the IgY brings benefits to case patients who do not receive SRP.

 

 

Immuno-intervention with immunoglobulin Y in alimentary tract infections as an alternative or adjunct to antimicrobials or vaccines

抗菌剤又はワクチンの代替又は補助剤としての消化管感染症における免疫グロブリンの免疫介入

Austin Journal of Clinical Medicine, 2014, 1(3); 1-3

Shofiqur Rahman, et al.

http://austinpublishinggroup.com/clinical-medicine/fulltext/ajcm-v1-id1012.php

It was only within the past quarter-century that interest surged over immunoglobulin Y (IgY) as an anti-infective clinical material unlike the more well-known mammalian immunoglobulin G (IgG) which has long been the workhorse of passive immunotherapy. IgY is the major immunoglobulin class of birds, amphibians, and reptiles, and possibly shares a common ancestor with mammalian IgE with which it has striking structural similarities. Among IgYs from the avian species, chicken IgY has historically been the most frequently described and studied. By immunizing poultry hens with any viral or bacterial antigen of interest, IgYs are generated in the systemic circulation and accumulate by default in the egg yolk from where they are collected and purified.

 

 

機能性卵黄リベチン(Immunoglobulin Yolk: IgY)による口腔ケア(特集 健康長寿を支える口腔ケア)(和)

Efficacy of functional livetin (Immunoglobulin Yolk: IgY) on oral infection

Food style 21, 2014, 18(3); 56-59

梅田浩二ら

https://www.foodchemicalnews.co.jp/item/cartfs21/813.html 雑誌

著者らはこれまでに、口腔感染症微生物(う蝕菌、歯周病菌、カンジダ菌)及び、腸管感染症病原体(ピロリ菌、腸管出血性大腸菌、ロタウイルス等)に対する鶏卵抗体の基礎研究と機能性食品等における有効性検証を含めた応用開発により、製品の実用化と共に多くの国際専門誌で論文発表している1~11)。本誌においても機能性卵黄リベチンとして紹介していただいているが1215)、歯周病に対する機能性卵黄リベチン(Immunoglobulin Yolk : IgY)の新しい研究結果を紹介する。リベチンとは、卵黄タンパク質に約30%含まれる卵黄水溶性タンパク質のことであり、α-β-及びγ-リベチンの3種類に分類される。γ-リベチンは血清γ-グロブリン(IgG)と同一である。

 

 

P.gingivalisジンジパインIgY抗体のラット実験歯周炎に対する歯槽骨吸収抑制効果 ()

The IgY antibody against P. gingivalis gingipains inhibits alveolar bone resorption on rat experimental periodontitis

神奈川歯学, 2014, 49(1); 16-23

鹿谷宗司:神奈川歯科大学感染制御学講座微生物分野

http://www.kdc-dent.js-md.net/Archive/ArticleDetail?full_dir=cn0kanas/2014/004901/003

Porphyromonas gingivalis (P.gingivalis), 黒色色素産生性のグラム陰性嫌気性桿菌であり, 歯周病患者のポケットから高率に分離されること, および本菌に対する血清抗体価が歯周炎患者血清において有意に高いことから, 歯周病発症に関わる有力な細菌の一つとされている. P.gingivalis, 唾液成分, 頬粘膜細胞, 赤血球, フィブロネクチン-コラーゲン複合物質および他の口腔細菌などに付着する性質を有しており, 本菌のヒト細胞への付着は, 歯周病発症の重要な第一歩であると考えられている. 更に, 糖尿病, 心臓血管疾患, 低体重児出産および誤嚥性肺炎などの全身疾患リスク因子としても注目されている. 本菌の病原因子の一つとして, 菌体表面および菌体外に強力なプロテアーゼを産生することが知られているが, なかでもジンジパイン(gingipains)は本菌の産生する主要なプロテアーゼであり, ペプチド切断部位特異性の異なるArg-gingipain (Rgp)Lys-gingipain (Kgp)が存在する.

Porphyromonas gingivalis has been implicated as an important pathogen in the development of adult periodontitis, and its colonization of subgingival sites is critical in the pathogenic process. The gingipains are cell surface Arg- and Lys-specific proteinases of the bacterium Porphyromonas gingivalis, which has been associated with periodontitis, a disease that results in the destruction of the teeth-supporting tissues. The aim of this study was to investigate the efficacy of egg yolk antibody against gingipains (IgY-GP) to the protection alveolar bone loss by P.gingivalis in rats. Rats were orally infected with P.gingivalis ATCC 33277, which was suspended in 5% carboxymethylcellulose. Each rat received 0.5 ml of the suspension by oral gavage. Then, the IgY-GP and the IgY-Control in 5% carboxymethylcellulose were administered, with each rat receiving 0.5 ml by oral gavage. The upper jaws were used as dry specimens for measuring horizontal alveolar bone loss. The distance between the cement enamel junction (CEJ) and the alveolar bone crest (ABC) was measured at 14 palatal sites per rat. P.gingivalis-infected group showed an increased distance between CEJ and ABC compared to uninfected group, indicating an enhanced alveolar bone loss due to oral infection with P.gingivalis. However, administered the IgY-GP group showed a decreased distance between CEJ and ABC compared to P.gingivalis-infected group. The IgY-GP could be used for the development of passive immunization against P.gingivalis-associated periodontal disease. These findings suggested that the IgY-GP protects P.gingivalis-induced alveolar bone loss.

 

 

Effects of oral moisturizing gel containing egg yolk antibodies against Candida albicans in older people

高齢者でカンジダ・アルビカンスに対する卵黄抗体を含有する経口保湿ジェルの効果

Gerodontology, 24 JUL 2014; DOI: 10.1111/ ger. 12139; 1-7

Susumu Takeuchi, et al.: Department of Community Dentistry, Tsurumi University School of Dental Medicine

http://onlinelibrary.wiley.com/doi/10.1111/ger.12139/abstract;jsessionid=C0830B44FEB315FF083F671BDC913762.f02t02

The aim of this study was to evaluate the inhibitory effects of oral moisturising gel containing egg yolk antibody against Candida albicans (anti-CA IgY) in older people. Therefore, we measured the number of Candia CFU present on oral swabs at baseline and after using the gel. A randomised, double-blind, placebo-controlled trial was conducted among volunteers living in a nursing home in Japan. The participants were divided into two groups. The group 1 participants received oral care using an experimental oral moisturising gel with anti-CA IgY, and those in group 2 received oral care using a placebo oral moisturising gel without anti-CA IgY. The oral care was performed by care workers three times a day for 4 weeks. The participants’ tongues were sampled using a swab method at baseline and after 2 and 4 weeks of using the oral gel, and the number of C.albicans, Candida tropicalis and Candida krusei colonies was counted. The baseline oral condition of the participants in the two groups did not differ significantly. The experimental gel significantly reduced the number of C.albicans colonies from baseline to after 4 weeks of using the oral gel; however, no significant reductions were observed in the number of C.tropicalis or C.krusei colonies. The use of oral moisturising gel containing anti-CA IgY for 1 month significantly reduces the number of C.albicans CFU present on swabs in older people.

 

 

Oral passive IgY-based immunotherapeutics: A novel solution for prevention and treatment of alimentary tract diseases

経口受動IgYベースの免疫療法: 消化管疾患の予防と治療のための新しい対策

Human Vaccine & Immunotherapeutics 9:5, 1039-1048; May 2013 Landes Bioscience

Shofiqur Rahman, et al.

https://pubmed.ncbi.nlm.nih.gov/23319156/

This commentary summarizes the laboratory investigations and clinical trials published recently involving per-oral application of IgY supplemented food for specific orogastrointestinal disease prevention and control purposes. The prolonged use and misuse of conventional antibacterial drugs has spawned antibiotic resistant microbes prompting scientists to search for other germ-killing options. In particular, the use of IgY as a novel mode of immunotherapy using oral chicken immunoglobulin (IgY) to confer passive immunity has gained much interest as an inexpensive non-antibiotic alternative for the prophylaxis and treatment of a wide variety of infectious diseases. The stability of IgY in the orogastrointestinal tract and its safety profile has been well-documented. IgY has been used in the treatment or prevention of dental caries, periodontitis and gingivitis, gastritis and gastric ulcer, oral thrush and infant rotavirus diarrhea. The recent clinical trials on IgY with encouraging results has catapulted into the market novel nutraceutical or health supplements for therapeutic or prophylactic intervention based on the consumption of mono-specific or mixed IgY formulations. With recent trends in consumer preference for natural materials to alleviate health concerns, the increasing healthcare costs and the recent advances in drug delivery systems, IgY is likely to shift from its mainly functional food status toward pharmaceuticalization in the foreseeable future.

 

 

機能性卵黄リベチン(Immunoglobulin Yolk: IgY)の高齢者口腔カンジダ症対策の研究(介護食:高齢者の栄養ケア)(和)

Efficacy of functional livetin (Immunogloblin Yolk: IgY) on elderly oral candidiasis (Nursing care food: Nutritional care for the elderly)

Food style 21, 2012, 16(3)

梅田浩二ら

http://sc.chat-shuffle.net/paper/uid:40019216224 雑誌論文

超高齢化社会を迎え長寿であることはとても素晴らしいことである。しかしながら、加齢に伴う体力や免疫力の低下、義歯の装着など何らかの体の衰えと上手に付き合いながら健康的な食生活を心がけなければならない。一方で、要介護者、各種病気の治療患者人口の増加による社会的問題があげられ、それとともに口腔ケアの重要性が認知されて各界で取り組みが行われている。今回取り上げる口腔の日和見感染症である口腔カンジダ症は、要介護者、抗菌剤、抗がん剤及ぴステロイド剤などの服用者、糖尿病息者、 ドライマウス患者、義歯装着者によくみられ、舌をはじめとする口腔粘膜に乳白色の苔状の偽膜、紅斑、潰瘍などが形成され、灼熱感、ヒリヒリ感、苦みや金属味を生じる。これらの症状は浅在性真菌症であるが、免疫能低下者にとって治療の機会を失うと短期に深部真菌症へと進展する。主な病原体はCandida albicansであり、義歯装着者ではCandida glabrataが関与することが多い。カンジダ菌は、口腔粘膜上皮細胞に付着、侵入し分泌型プロテアーゼ酵素類によってさまざまな炎症を引き起こす。口腔カンジダ菌に関連する口腔粘膜疾患は、免疫能低下者に対して予防的に抗真菌薬が使用されているが、おおくは発症後に抗真菌薬を治療として使用する。紹介する機能性卵黄リペチンは、食品として摂取することで口腔内のカンジダ菌を排除して口腔粘膜疾患を予防する機能性食品原料であり、その作用機序と効果について述べる。

 

 

新機能抗体開発ハンドブック(和):第7編 ニワトリ卵黄免疫グロブリン(Immunoglobulin yolkIgY)の産業への利用(第1 概論、第2 IgYのエアフィルターへの応用、第3 機能性食品への応用と可能性、第4 今後の展望)

Handbook of Therapeutic and Diagnostic Antibodies: Volume 7: Industrial use of chicken egg yolk immunoglobulin (Immunoglobulin yolk: IgY). (Chapter 1 Introduction. Chapter 2 Application of IgY to air filters. Chapter 3 Application and possibility to functional foods. Chapter 4 Future outlook.)

新機能抗体開発ハンドブック エヌ・ティー・エス, 20128, 591-603

児玉義勝ら

http://www.nts-book.co.jp/item/detail/summary/bio/20120800_95.html 本

ブタの初乳にはIgG と分泌性IgA が大量に含まれている。子ブタが生後48 時間以内に初乳を摂取するとIgG は腸管絨毛上皮細胞から吸収されて血中IgG(移行抗体)となり,全身性感染症の防御に働き,また分泌性IgA は腸管粘膜にとどまり局所感染症を防御する。子ブタはこのように初乳によってのみ,免疫グロブリンの母子移行が起こる。鳥類では親鶏の生んだ卵の卵黄成分に含まれる免疫グロブリン(IgY)を胎児が吸収することにより孵化したヒナに母子移行が成立する。特異的IgYの作成は鳥類に備わっている「卵黄内への輸送機能」の生物学的な仕組みを利用する。これは目的とするターゲット抗原を親鶏に接種することで,血清中に接種抗原に対する免疫グロブリンが産生され,それを卵黄に蓄積して産卵する。親鶏に接種する抗原の種類を変えるだけで,特異性の異なるいろいろなIgYが生産できる。このIgYは,哺乳類のIgG に相当するもので分子サイズは大きく180 kDaであるがH鎖不変領域は4個のドメインからなり,H鎖は哺乳類IgGと異なる。

 

 

Anti-cell-associated glucosyltransferase immunoglobulin Y suppression of salivary mutans streptococci in healthy young adults

健常若年成人における抗菌体結合型グルコシルトランスフェラーゼ鶏卵抗体による唾液中ミュータンスレンサ球菌の抑制

The Journal of the American Dental Association, 2011, 142(8); 943-949

Sa V. Nguyen, et al.

http://jada.ada.org/article/S0002-8177(14)62069-9/references

The authors evaluated the suppressive effects of lozenges containing egg yolk antibodies (that is, immunoglobulin Y [IgY]) against Streptococcus mutans cell-associated glucosyltransferase (CA-gtf) on oral colonization by mutans streptococci (MS) in healthy young adults. In a five-day double-masked placebo-controlled trial, young adult participants self-administered lozenges containing anti–CA-gtf IgY (Ovalgen DC, GHEN, Gifu-City, Japan) or a placebo at prescribed times each day. On the basis of bacterial colony counts of saliva cultures, the authors analyzed the pretrial and posttrial differences in levels of MS and total anaerobic bacteria among participants in the treatment (anti–CA-gtf IgY) and placebo groups and a control group. Salivary MS scores in participants in the treatment group decreased significantly (P < .001), and the mean anaerobic bacterial count in the treatment group was not statistically different before and after the trial. In the placebo and control groups, posttrial changes in median MS scores and total salivary anaerobic bacterial counts were not statistically significant. The results of the study show that lozenges containing anti–CA-gtf IgY can suppress oral colonization by MS in healthy young adults. Lozenges containing anti–CA-gtf IgY may help reduce dental caries risk in humans.

 

 

Effect of IgY against Candida albicans and Candida spp. adherence and biofilm formation

カンジダ・アルビカンスとカンジダ属の付着力とバイオフィルム形成力に対するIgYの効果

Japanese Journal of Infectious Diseases, 2009, 62(5): 337-342

Taisuke Fujibayashi, et al.: Dentistry for Persons with Disabilities, Tokyo Medical and Dental University

https://pubmed.ncbi.nlm.nih.gov/19762981/

https://www.niid.go.jp/niid/images/JJID/62/337.pdf

The fungal pathogen Candida albicans is an opportunistic fungal pathogen that causes oral and vaginal mucosal infections as well as systemic disease. The ability of C.albicans to adhere to host surfaces is positively correlated with its pathogenicity. We prepared a polyclonal anti-Candida albicans antibody in chicken egg yolk (anti-C.albicans IgY) and investigated its in vitro effectiveness in preventing C.albicans adherence and biofilm formation. Anti-C.albicans lgY significantly reduced the adherence of C.albicans SC5314 to human oral epithelial cells in a dose-dependent manner. The same effect was also observed in other Candida spp. including C.albicans serotype A and B. Further, the IgY inhibited biofilm formation of C.albicans in medium without serum, but the inhibition was slightly restored in medium conditioned with 10% serum. The data indicate that anti-C.albicans IgY cross-reacted with various Candida spp. and may have a protective effect against oral candidiasis and reduce the dissemination of Candida spp. This effect may be due to the blocking of the binding of Candida spp. to the host cells. However, the blocking did not play a role when Candida formed a germ tube in the presence of serum. Therefore, anti-C.albicans lgY may be considered as a prophylactic immunotherapy or possibly an adjunctive antifungal therapy under limited conditions.

 

 

In vitro and in vivo effectiveness of egg yolk antibody against Candida albicans (anti-CA IgY)

抗カンジダ・アルビカンス鶏卵抗体のin vivoおよびin vitroにおける効果

Vaccine, 2008, 26(17); 2073-2080

Ibrahim el-SM, et al.

http://www.sciencedirect.com/science/article/pii/S0264410X08002326

We prepared anti-Candida albicans antibody in chicken egg yolk (anti-CA IgY) and investigated its in vitro and in vivo effectiveness. Anti-CA IgY significantly reduced the adherence capacity of C. albicans to FaDu cells (human pharynx carcinoma cells) in a dose-dependent manner. The protective efficacy of anti-CA IgY was investigated in experimentally induced oral candidiasis in immunosuppressed mice. Oral administration of anti-CA IgY significantly reduced the number of C. albicans and the scores of the tongue lesions. Moreover, anti-CA IgY reduced the colonization of C. albicans in mice organs. These results indicate that anti-CA IgY has a protective effect against the oral candidiasis of experimentally infected mice and reduces the dissemination of C. albicans. Putting together, these results indicate that anti-CA IgY is effective against C. albicans. This effect might be due to the blocking of the binding of C. albicans to the host cells. Therefore, anti-CA IgY might be considered as a prophylactic immunotherapy or possibly an adjunctive antifungal therapy.

 

 

Effect of egg yolk antibody against Porphyromonas gingivalis gingipains in periodontitis patients

歯周病患者における抗ポルフィロモナス・ジンジバリス ジンジパイン鶏卵抗体の効果

Journal of Oral Science, 2007, 49(3); 201-206

Kyosuke Yokoyama, et al.: Department of Periodontology, Nihon University School of Dentistry

https://www.jstage.jst.go.jp/article/josnusd/49/3/49_3_201/_article

https://www.jstage.jst.go.jp/article/josnusd/49/3/49_3_201/_pdf

Porphyromonas gingivalis gingipains is suspected to be one of the most important causative agents of periodontitis. We postulated that the inhibition of gingipains may reduce the pathogenic nature of P.gingivalis. Anti-P.gingivalis egg yolk antibody (IgY-GP) was isolated from the yolks of hens immunized with purified gingipains. We applied IgY-GP gel sub-gingivally in periodontitis patients who harbored P.gingivalis in their subgingival flora. Five pairs of contralateral anterior single-rooted teeth were selected. One tooth in each contralateral pair was randomly treated with IgY-GP and subgingival scaling and root planning, whereas the other tooth was treated with SRP alone. The number of P.gingivalis bacteria was assessed by real-time PCR. Bacterial levels were expressed as the percentage of total bacteria. The IgY-GP group had a significant reduction in probing depth. BOP significantly decreased in the IgY-GP group compared to the control group at week 4. The levels of P.gingivalis significantly increased in the control group at week 4, whereas the reduction in the levels of P.gingivalis was sustained in the IgY-GP group. Within the limitations of the present study, IgY-GP was shown to be an effective immunotherapeutic agent in the treatment of periodontitis.

 

 

抗ジンジパイン鶏卵抗体含有タブレットの臨床的および細菌学的評価 ()

Clinical and bacteriological evaluation of anti-gingipain egg yolk antibody

日本歯科保存学雑誌, 2007, 50(3); 358-364

瀧川智子ら:日本大学院 応用口腔科学分野

https://www.jstage.jst.go.jp/article/shikahozon/50/3/50_KJ00005459793/_article/-char/ja

グラム陰性の偏性嫌気性菌であるPorphyromonas gingivalisは,歯周病の最も有力な原因菌であると考えられている。P.gingivalisの産生するジンジパインは,発育増殖に不可欠な因子であると同時に,宿主タンパクを広範に分解し宿主免疫機構の破綻をきたす重要な病原因子である。本研究では,ジンジパインを標的とした受動免疫による歯周病治療の可能性について検討した。ジンジパイン抗原を免疫した鶏卵から抽出した抗ジンジパイン鶏卵抗体(lgY-GP)を含有するタブレットを調製し,被験者に8週間投与したその結果,投与前後で臨床症状に顕著な変化は認められなかったが,細南学的評価では,唾液中の総細菌数に対するP.gingivalisの割合がlgY-GP含有タブレットを服用した群で統計学的に有意に減少した。今後,さらにlgY-GPの有用性を明らかにし,効果的な使用方法を確立するために,さらなる研究が必要であると考えられる。

Prophyromonas gingivalis, a Gram-negative anaerobe, has been identified as an important periodontal pathogen. Gingipains from P.gingivalis play a major role in not only bacterial housekeeping but also inactivation of host defenses. In this study, we investigated the effect of anti-P.gingivalis egg yolk antibody against gingipains (IgY-GP) in human volunteers for 8 weeks. IgY-GP administration did not cause a significant change in clinical parameters. However, P.gingivalis levels in saliva were significantly decreased. Further studies are needed to clarify the usefulness of IgY-GP and the clinical application for periodontal disease.

 

 

歯周病患者における抗ジンジパイン鶏卵抗体の臨床的および細菌学的評価(和)

Clinical and bacteriological evaluation of anti-gingipain egg antibody in patients with periodontal disease

日大歯学(Nihon University Dental Journal), 2007, 81(1); 51-56

横山京介ら:日本大学大学院歯学研究科歯科臨床系専攻

http://www2.dent.nihon-u.ac.jp/nusdj/zasshi/j-zas81.htm 雑誌

国民の大多数が罹患している口腔感染症である。グラム陰性の偏性嫌気性菌であるPorphyromonas gingivalis (P.gingivalis) は,歯周病の最も有力な原因菌であると考えられている。P.gingivalisの産生するジンジパインは,口腔環境内で発育増殖していくために不可欠な因子であると同時に,宿主タンパクを広範に分解し宿主免疫機構の破綻をきたす重要な病原因子とされている。そこで本研究では,ジンジパイン抗原を免疫した鶏卵から鶏卵抗体(IgY-GP) 含有タプレットを調整した。被験者にlgY-GP含有タプレットを2週間投与し,その前後での臨床的, 細菌学的評価を行った。その結果,プロービング時の出血(bleeding on probing, BOP), 歯周ポケット深さ(probing depth, PD),最深部PDおよびプラークコントロールレコード(plaque control record, PCR) に顕著な変化は認められなかった。細菌学的評価は投与前後の唾液を採取し,real-time polymerase chain reaction (real-time PCR) 法を用いて総細苗数に対するP.gingivalis の割合で求めた。lgY-GP群では著明な変化は認められなかった。本研究期間中に副作用が認められなかったことから安全性は期待できるが,その効果を明らかにするために,今後研究デザインの検討が必要である。

 

 

Activity of anti-Porphyromonas gingivalis egg yolk antibody against gingipains in vitro

in vitroにおけるジンジパインに対する抗ポルフィロモナス・ジンジバリス鶏卵抗体活性

Oral Microbiology Immunology, 2007, 22; 352-355

Yokoyama K, et al.

http://onlinelibrary.wiley.com/doi/10.1111/j.1399-302X.2007.00358.x/abstract

We investigated the effect of anti-Porphyromonas gingivalis egg yolk antibody against gingipains [immunoglobulin Y (IgY)-GP] on gingipain activity in vitro. IgY-GP was isolated from the yolks of White Leghorn hens immunized with purified gingipains. Control antibody (IgY) was isolated from the yolks of non-immunized hens. Gingipain activity was assessed according to the rate of enzymatic substrate hydrolysis. Human epithelial cells were cultured with or without gingipains and with gingipains pretreated with either IgY-GP or IgY. Hydrolytic activity decreased in the presence of IgY-GP. Cells incubated with gingipains showed a dose-dependent loss of adhesion activity. Pretreatment of gingipains with IgY-GP was associated with strong inhibition of cell detachment, whereas pretreatment with IgY was not. Our findings suggest that IgY-GP may be an effective immunotherapeutic agent in the treatment of periodontitis.

 

 

ベビーフードと子供用サプリメント: Streptococcus mutansグルコシルトランスフェラーゼ鶏卵抗体を配合したオーラルケア用サプリメントの開発 ()

Baby food and children's supplements: Development of supplement containing anti-Streptococcus mutans glucosyltransferase chicken antibody for oral care

Food style 21 2007, 11(9): 53-55

佐藤冬彦ら:ファーマフーズ

歯は体の他の器官と違い、虫歯にかかってしまうと自然に治癒することはない。欧米では虫歯は「治療」より「予防」という考え方が基本である。しかし日本では虫歯予防の臨床への浮入が遅れており、効果的な虫歯予防の手段が求められている。現在、小学生の時点での日本人の虫歯罹患率は6~7割であり、この数字は年々減少傾向にあるがいまだ多くの子供が虫歯に罹患している。大人の歯に比べ、子供の歯は歯質が弱く虫歯にかかりやすい。その上、乳歯時の虫歯はその後の歯並びやかみ合わせにも悪影響を及ぼすことが明らかにされている。虫歯とはストレプトコッカス・ミュータンス菌(Streptococcus mutans)に代表される虫歯原因菌による口腔内感染症であるが、これら虫歯原因菌は出産直後の乳児の口腔内には見られない。ミュータンス菌等の虫歯原因菌は、乳歯崩出の時期(19カ月から31カ月)に母親の唾液等を介した母子感染経路を主として後天的に感染することが知られている。したがって子供の虫歯予防は早くから始められるべきであり、さらにその感染源である母親の歯のケアを同時に行うことも重要である。そこで我々は母と子の虫歯予防のために「鶏卵抗体」(以下、IgY)に注目した。これは「たまご」(鶏卵)を用いて作り出す抗体であり、安全性の高い機能性食品素材として幼児から大人まで幅広い使用が可能である。本稿では、鶏卵抗体技術の概要と本技術を応用して作られた抗虫歯機能を持った抗体高含有食品素材「Ovalgen DC」、さらに本素材を用いた抗虫歯サプリメントの開発について紹介する。

 

 

歯・口腔ケアと健康: 鶏卵抗体IgYを利用した口腔ケア(和)

Teeth / oral care and health: Oral care using chicken egg antibody IgY

Food style 21, 2007, 11(2); 1-4

磯田理絵ら

http://sc.chat-shuffle.net/paper/uid:40015216093 雑誌検索

動物は、外部から侵入してくる細菌やウイルス等の異物に対して「抗体」と呼ばれるたん白質を血液中に産生し、細菌やウイルスに対抗する自己防御システムを有している。哺乳動物の場合、親が獲得した特異抗体を胎盤や母乳を通して子に移行させることにより、子を病原体から守

っている。しかしながら鳥類は胎盤も母乳も持たない。そこで親烏は、自らが獲得した血液中の特異抗体を卵に移行させることにより、ヒナを病原体から守っているのである。この親鳥から卵に移行された抗体は、特に親烏の血液中lgGが卵黄(Yolk)に蓄積されることから、Immunoglobulin YolkすなわちlgYと呼ばれる。この烏類に特有な免疫システムを利用することにより、様々な抗原に対して特異的な抗体を大量生産することが可能となった。本稿では、この技術を利用した鶏卵抗体を応用して口腔内感染症を予防する機能性食品素材Ovalgenについて紹介する。

 

 

たまごの健康機能と開発応用:S.mutans CA-GTaseに対するIgYを用いた経口受動免疫によるう蝕予防(和)

Egg health function and development application: Prevention of caries by oral passive immunity using IgY for S.mutans CA-GTase

Food style 21, 2006, 10(3); 1-3

児玉義勝

動物は、外部から侵入してくる病原体等の異物に対して「抗体」というたん白質を血液中に産生することにより、自己防御システムを築いている。哺乳動物の場合、親が獲得した抗体を胎盤や母乳を通して子孫を病原体から守っている。しかし烏類は胎盤も母乳も持たないため、親鳥が獲得した血液中の抗体は主に卵黄中に移行蓄積される。この卵黄中の抗体を、卵黄(Yolk)にちなんでImmunoglobulin (=抗体)YolkすなわちIgYと呼ぶ。

 

 

鶏卵の科学とその利用:鶏卵卵黄抗体(IgY)と感染症予防(和)

Science on Eggs and It‘s Utilization: Oral passive immunization by chicken egg yolk antibodies against urease of Helicobacter pylori and cell-associated glucosyltransferase of Streptococcus mutans

Food & Food Ingredients Journal of Japan, 2006, 211(11); 939-947

児玉義勝

生まれた仔プタや仔ウシが初乳を介して母体が持っている抗体(IgG)を大量に摂取することにより、 口腔から侵入する病原体から身を守るという仕組みがある。しかし母乳を持たないトリでは、卵の卵黄が家畜の初乳に相当し、そこに親鳥からのIgGが卵黄抗体(IgY)として蓄積される。ヒナは卵黄からIgYを吸収した状態でふ化するため、ふ化後のヒナはその抗体で病原体から を守るのである。この鳥類に特徴的なIgYの母子間移行システムをバイオ工場として利用することが出来る。IgYの有用性について、ヒトに惑染し胃炎・胃沿瘍を引き起こすといわれているピロリ菌の例を挙げる。親鳥に、ピロリ菌が胃内定着に関与する菌体外膜タンパク(抗原)を数回注射すると、親鳥体内で抗原に対する特異的な抗体が作られ、それがlgYとして卵黄に移行し、蓄積する。このIgYをビロリ菌保有者が摂取すると、ピロリ菌の外膜タンパクにlgYが特異的に結合することによって定着が阻害される。このような仕組みと効果を経口受動免疫という。lgYの特徴とメリットは、1羽の親屈は1年問に約300個の卵を生むため、その卵黄から効率よくlgYが回収できる。哺乳類のlgGと比較して、IgYは抗原抗体結合力(アフィニティー)が約10倍強い。鶏病予防の目的で、連綺的なワクチネーションの方法が確立している。大羽数飼育技術が確立している。食品としての液卵ならびに粉卵の生産方法はすでに工業化されている。抗原の種類を変えるだけで、特異性の異なるlgYを一本の生産ラインで製造できる。が挙げられる。消化管粘膜をターゲットとしたユニークな特徴を有するlgYを利用した経口受動免疫療法はlgY含有食品を摂取することによって、う蝕、歯周炎、アレルギー、肥満、ピロリ菌による胃炎、原因不明な炎症性疾患などの問題を改善できると考えられる。本稿では、IgYによるピロリ菌の接着阻害とミュータンス菌のグルカン合成抑制について述べる。

Chicken egg yolk antibody possesses several merits over other antibodies due to its more specific immuno-reactivity i.e. less cross reactivity with mammalian proteins, being inexpensive, and its continuous and most humane way of producing enormous amounts without sacrificing the chicken. A chicken usually lays about 280 eggs in a year, and egg yolk contains 100-150 mg of lgY per yolk, suggesting that more than 40 g of lgY per year can be obtained from each chicken through eggs. Passive immunization by oral administration of specific antibodies has been an attractive approach against a variety of pathogens in both humans and animals. Helicobacter pylori (H. pylori) is known to be a major pathogenic factor in the development of gastritis, peptic ulcer diseases and gastric cancer in humans. H. pylori adheres and colonizes the surface of gastric mucosa using the functions of its urease. Egg yolk antibody developed against urease efficiently blocked the binding site of H. pylori to its specific mucin receptor in the gastric mucosa. So, oral administration of urease-specific lgY not only inhibited disease activity but also prevent de novo colonization in gastric mucosa, in those sites not yet infected. These encouraging results may pave the way for a novel therapeutic and prophylactic approach in the management of H. pylori-associated gastroduodenal disease. Streptococcus mutans plays an important role in the development of dental caries in humans. Major virulence factor cell-associated Glucosyltransferase (CA-GTase) degrades sucrose to form insoluble glucan, which serves as a bridge for the bacterium to bind tightly to the tooth surface. After binding of S.mutans, it release large amount of acids by fermenting a variety of sugars from the diet, which decalcify enamel, thus causing tooth decay or dental caries. Chicken anti-CA-GTase antibody effectively blocks the CA-GTase from binding to the tooth surfaces, thus inhibiting its growth and preventing the development of dental caries. Anti-CA-GTase antibody also inhibits the synthesis of insoluble glucan by the enzyme, thus assisting with the elimination of the bacterium from the oral cavity. Additionally, the use of specific antibodies (lgY) in controlling other oral microflora e.g. Porphyromonas gingivalis and Candida albicans are also taken into consideration because recent developments indicate a promising future.

 

 

The Effects of Egg-Derived Antibodies to Glucosyltransferases on Dental Caries in Rats

グルコシルトランスフェラーゼに対する卵由来抗体のラットのう蝕における効果

Caries Research, 2004(1), 38; 9-14

C. Kruger, et al.: Center for Oral Biology, Karolinska Institutet and Division of Clinical Immunology, Karolinska Institutet

https://www.karger.com/Article/Abstract/73914

The role of Streptococcus mutans in the development of dental caries is well recognized. Important virulence lac-tors include the glucosyltransferases (gtf), essential for production of glucans. We evaluated the anticariogenic effects of orally administered chicken anti-cell-associated (CA) Gtf antibodies in desalivated rats. The animals were infected with S. mutans MT8148R and treated with chicken anti-CA-Gtf egg yolk antibodies (lgY) or nonimmune egg yolk powder. Smooth surface lesions were significantly lower in the anti-CA-Gtf-treated group in comparison to the control groups. Sulcal surface caries was also decreased and of less severity. Our study suggests that chicken anti-CA-Gtf antibodies may have promise as a prophylaxis for high caries risk patients.

 

 

Passive Immunity for Protection against Mucosal Infections and Vaccination for Dental Caries

粘膜感染症に対する防御のための受動免疫とう蝕のためのワクチン接種

Mucosal Vaccines, 1996, Academic Press, Inc.; 187-197

Shigeyuki Hamada, et al.: Department of Oral Microbiology, Osaka University Faculty of Dentistry

http://store.elsevier.com/product.jsp?isbn=9780124105805&pagename=search  Book

A variety of innate and acquired defense mechanisms exist that protect the host from potential pathogenic microorganisms. The outcome of a particular infection depends on interactions between the virulent capability of the pathogen to evade and damage the host as well as the degree of adaptive immune responses in the host. The adaptive immune response is quiescent until stimulated by immunizing events, usually infections. Vaccination is the intentional process that can stimulate adaptive resistance in the host by enhancing humoral immune responses. Since a variety of microbial infections occur at the mucosa or penetrate through mucosal surfaces of the body, induction of antibodies in the mucosa is desirable in vaccinations. Since it is frequently difficult to induce sufficient immunoglobulin levels for protecting the host following current immunization procedures, passive immunization may be considered as an alternative measure for controlling infectious diseases in humans and animals. Use of egg yolk antibodies from hens immunized by specific virulence factors or micro-organisms may provide a novel approach to the control of infectious disease; this approach is reviewed in this chapter.

 

 

Lack of cross-reaction of antibodies against cell-associated glucosyltransferase from Streptococcus mutans with human heart tissue

ストレプトコッカス・ミュータンス由来の菌体結合型グルコシルトランスフェラーゼに対する抗体とヒトの心臓組織との交差反応性は無い。

Advances in Mucosal Immunology, 1995. Plenum Press, New York; 1161-1165

TAKASHI IWASE, et al.: Department of Pathology, Nihon University School of Dentistry

Production of glucan from sucrose by glucosyltransferases (GTases) is essential for adherence of Streptococcus mutans to the tooth surface, and may lead to the development of dental caries. We recently isolated and characterized cell-associated (CA)-GTase of S.mutans MTS 148 (serotype c) that synthesizes insoluble glucan from sucrose. Furthermore, we have found that oral passive immunization with the egg yolk antibody specific for CA-GTase resulted in a reduced severity of dental caries in S.mutans-infected rats. It is well known that strains of S. pyogenes, the causative agent of rheumatic heart disease, possess antigens that cross-react with heart tissue. Often reports indicated that rabbit antisera against S.mutans whole cells may cross-react with human and monkey heart tissue. However, different findings of immunofluorescence stainings were reported by various investigators and this cross-reactivity induced by S.mutans-related antigens has not been elucidated. In this study, we investigated the ability of yolk antibody against CA-GTase to cross-react with human heart tissue by ELISA and immunohistochemical method.

 

 

卵黄抗体を用いた齲蝕の受動免疫 ()

Passive immunity against dental caries by use of hen egg yolk antibody

歯界展望, 1992, 79(7); 1619-1624

大嶋隆ら:大阪大学歯学部 小児歯科学講座

ニワトリを免疫するとlgG抗体が卵黄で選択的に濃縮されることが知られている。齲蝕原生細菌Streptococcus mutansの病原性を担うと考えられている不溶性グルカン合成酵索(CA-GTase)を抗原としてニワトリに免疫を行ったところ、特異的で,高力価を示す卵黄抗体が得られた。この卵黄抗体は.S.mutans 菌体を凝集させるだけでなく、CA―GTaseによる不溶性グルカンの合成とS.mutans 菌体の平滑面付着を抑制した。また、この卵黄抗体を飼料および飲料水中に添加して投与すると,ラットにおけるS.mutans 誘発齲蝕を有意に抑制した。これらの結果は、CA-GTaseに対する卵黄抗休による経口受動免疫が、齲蝕の予防に有効な手段となりうることを強く示唆している。

 

 

Antigens of Streptococcus mutans and oral passive immunization against dental caries with egg yolk antibodies to the antigens

ストレプトコッカス・ミュータンスの抗原とその坑原に対する鶏卵抗体を用いたう蝕に対する経口受動免疫

Frontiers of Mucosal Immunology. Volume 1., 577-580, 1991, Tsuchiya et al. eds. (Proceedings of the Sixth International Congress of Mucosal Immunology), Elsevier Science Publishers

HAMADA SHIGEYUKI, et al.: Department of Oral Microbiology, Osaka University Faculty of Dentistry

Streptococcus mutans and Streptococcus sobrinus are two 'mutans' group of streptococci that were once referred collectively to as "Streptococcus mutans". Strains of the "S.mutans" group were classified into serotypes a through h. In the past decade, the use of DNA relatedness has indicated that the "S.mutans” group embraces seven separate species including S.mutans and S.sobrinus. The natural niche of S.mutans is found to be on the tooth surface. The abilities of S.mutans to adhere very firmly to the tooth in the presence of sucrose, and to form acids by fermentation of sugars are factors forming the foundation of its virulent cariogenic potential. Some strategies to block the virulence factors of S.mutans have been attempted by the elimination or reduction of the organisms from the oral cavity of man, expecting the prevention of dental caries development. Reductions in dental caries experimentally induced by S.mutans or S.sobrinus have been shown after active immunization procedures or after passive administration of antibody to the antigens of these mutans streptococci. In this short review, we summarize the cellular and extracellular components of S.mutans that may participate in the adherence of the organism to the tooth surface, and the protection of rats against dental caries by passive immunization with specific antibodies to S.mutans antigens.

 

 

Oral passive immunization against dental caries in rats by use of hen egg yolk antibodies specific for cell-associated glucosyltransferase of Streptococcus mutans

ストレプトコッカス・ミュータンスの菌体結合型グルコシルトランスフェラーゼに対する鶏卵特異抗体によるラットう蝕実験に対する経口受動免疫

Infection and Immunity, 1991, 59(11); 4161-4167

HAMADA SHIGEYUKI, et al.: Department of Oral Microbiology, Osaka University Faculty of Dentistry

http://iai.asm.org/content/59/11/4161

The effect of polyclonal egg yolk immunoglobulin G antibodies (yIgG) raised against whole cells, cell-free (CF) glucosyltransferase (GTase), or cell-associated (CA) GTase of serotype c Streptococcus mutans was examined in terms of in vitro inhibition of virulence-related factors of S.mutans and protection of S.mutans-infected rats against the development of dental caries. Hens (18 weeks old) were immunized with formalin-treated whole cells, purified CF-GTase, or CA-GTase together with Freund's complete adjuvant. In addition, yIgG to surface protein antigen was used in some in vitro experiments for comparison with other antibodies. yIgG was purified by ammonium sulfate precipitation followed by DEAE-Sephacel column chromatography or fractional precipitation with ethanol. Purified yIgG was found to be a 220-kDa protein, which was dissociated into heavy and light chains upon addition of 2-mercaptoethanol. yIgG to whole cells and surface protein antigen gave a heavy aggregation of S.mutans organisms, while yIgG to CF- and CA-GTase specifically inhibited the enzymatic activity of the respective GTase. yIgG to CA-GTase and whole cells was found to clearly suppress the adherence of S.mutans cells to a glass surface. Specific-pathogen-free Sprague-Dawley rats that had been infected heavily and repeatedly with S.mutans and fed diet no. 2000 developed severe dental caries, while rats fed diet 2000 containing greater than or equal to 0.1% yIgG to CA-GTase showed a statistically significant reduction in dental plaque accumulation and caries development. Administration of yIgG to CF-GTase and whole cells failed to protect against caries. These results clearly suggest that yIgG to S. mutants CA-GTase specifically inhibited a virulence factor of this organism, i.e., insoluble glucan-synthesizing CA-GTase, resulting in a significant reduction in the development of dental caries.

 

 

口腔免疫とはなにか: Streptococcus mutansの抗原成分とう蝕免疫 ()

What is oral immunity?:  Antigenic components of Streptococcus mutans and caries immunity.

歯科ジャーナル 1990,31(6):739-747The Journal of dental medicine

浜田茂幸ら:大阪大学歯学部細菌学教室

Streptococcus mutansが実験動物においてう蝕を誘発することが明らかにされてから30年になる。当然のことながら,感染症としてのう蝕を免疫学的に予防すべく多くの研究が試みられてきた。しかし, う蝕は歯という硬表面(solid surface)が発病の場であり,血液の循環を受けていない。その代わり,歯面は唾液で被われており,歯肉溝では歯肉溝液が滲出し,同液が歯面を歯頸部から咬合面へかけて潤している。歯肉溝液は循環血液の血清成分が滲出したものと考えられ,lgGをはじめ,lgA, lgMなどの抗体を含む。血球成分も出現し,食作用などの機能を果たしている。一方,唾液は1日に約1.5リットル分泌され,唾液中には他の外分泌液と同様にlgA,特に分泌型lgA(slgA)の占める割合がIgGlgMに比して多い。口腔におけるslgAの関与は他の粘膜部位と同じで,その意味では口腔は粘膜免疫(mucosal immunity)の発現の大きな場ということになる。う蝕の予防を免疫学的手段を駆使して達成することは研究者の夢である。そのためにはう蝕原性細菌(cariogenic bacteria)の発病要因を抑制する免疫抗体を適切に生体内で誘導するか,あるいは体外で別途調製した抗体を宿主に受動的に与える方法を開発しなければならない。

 

 

Purification and characterization of cell-associated glucosyltransferase synthesizing water-insoluble glucan from serotype c Streptococcus mutans

血清型cタイプのストレプトコッカス・ミュータンスが産生する不溶性の菌体結合型グルコシルトランスフェラーゼの精製と性状

Journal of General Microbiology, 1989, 135; 335-344

Shigeyuki Hamada, et al.: Department of Oral Microbiology, Osaka University Faculty of Dentistry

https://www.microbiologyresearch.org/docserver/fulltext/micro/135/2/mic-135-2-335.pdf?expires=1629783005&id=id&accname=guest&checksum=691B4102F3B153A16CBBC0560FA49473

Strains of Streptococcus mutans (serotypes c, e and f) were found to possess high levels of glucosyltransferase (GTase) activity, both cell-associated and in the culture medium, when grown in either sucrose-free or sucrose-containing broth media. The cell-associated GTase of S.mutans MT8148 (serotype c) was effectively extracted by treatment with 8 M-urea at 25 "C for 1 h. Approximately 95% of the GTase activity was solubilized by this treatment. The crude extract was purified by DEAE-Sephacel and hydroxyapatite column chromatography. For comparison, extracellular GTase was also purified from the culture supernatant of the same strain by ammonium sulphate precipitation, chromate-focusing and hydroxyapatite chromatography. The molecular masses of the cell-associated and extracellular GTase proteins were similar (156 kDa) as determined by SDS-PAGE. However, the pH optima for maximum GTase activity were different: pH 6.7 to 7.0 for the cell-associated enzyme and pH 5.5 to 6.5 for the extracellular enzyme. The product of cell-associated GTase from sucrose was almost exclusively water-insoluble glucan. On the other hand, extracellular GTase produced mainly water-soluble glucan from sucrose. This indicates that GTase synthesizing water-insoluble glucan is present primarily in a cell-associated form in serotype c S.mutans. Insoluble glucan synthesis by the cell-associated GTase from sucrose was not enhanced by addition of primer dextran T10 to the reaction mixture. The extracellular and cell-associated GTases were immunologically unrelated as determined by ELISA using monoclonal antibodies.




<GI care>


Synergistic effect of anti-Helicobacter pylori urease immunoglobulin Y from egg yolk of immunized hens and Lactobacillus johnsonii No.1088 to inhibit the growth of Helicobacter pylori in vitro and in vivo.

インビトロとインビボ試験においてヘリコバクター・ピロリ菌の増殖抑制する免疫鶏の卵黄由来のヘリコバクター・ピロリ菌のウレアーゼに対する免疫グロブリンYLactobacillus johnsoni No.1088 の相乗効果。

Vaccine 37 (2019) 3106-3112

Yiji Aiba, et al.: Development Reserch Department, Snowden Co., Ltd.

https://www.sciencedirect.com/science/article/pii/S0264410X19305092?via%3Dihub

Helicobacter pylori is a pathogenic bacterium that infects the stomach, causing chronic gastritis; and it is also considered to be related to the occurrence of gastric cancers. Although some eradication regimens including multiple antibiotics have been developed, the emergence of resistance to antibiotics becomes problematic. Therefore, other approaches to compensate or augment the effects of standard regimens are needed. In this study, we examined the possible synergistic effects of anti-H. pylori urease IgY and Lactobacillus johnsonii No.1088 (LJ88) both in vitro and in vivo. Anti-H. pylori urease IgY was purified from egg yolks laid by the hens immunized with urease purified from H. pylori. LJ88 is a unique strain of lactic acid bacterium isolated from human gastric juice, and it has been reported to inhibit H. pylori both in vitro and in vivo. The in vitro mixed culture study showed that anti-H. pylori urease IgY augmented the anti-H. pylori activity of LJ88 against both clarithromycin-sensitive and -resistant H. pylori strains. In a germ-free mice infection model, combined administration of daily anti-H. pylori urease IgY and weekly living LJ88 significantly reduced H. pylori infections, whereas either monotherapy did not. In an in vivo human gut microbiota-associated mice model, not only daily administration of living LJ88 but also heat-killed one significantly reduced an H. pylori infection in the stomach when combined with anti-H. pylori urease IgY. The extent of reduction of the stomach H. pylori by such a combination therapy was larger than that reported for LJ88 monotherapy. These results taken together revealed a synergistic effect of anti-H. pylori urease IgY and living or heat-killed LJ88, thus suggesting that such a combination might be a promising therapy to possibly compensate and/or augment standard anti-H. pylori regimens.

 

 

Chicken Egg Yolk Antibodies (IgY) for Prophylaxis and Treatment of Rotavirus Diarrhea in Human and Animal Neonates: A Concise Review.

ヒトと幼獣のロタウイルス下痢症の予防と治療のための鶏卵抗体(IgY):総説

Korean Society for Food Science of Animal Resources, 2017, 37(1); 1-9

Hlaing Myat Thu, et al.: Department of Medical Research, Myanmar

http://koreascience.or.kr/article/JAKO201711656579331.page

http://koreascience.or.kr/article/JAKO201711656579331.pdf

The rotavirus-induced diarrhea of human and animal neonates is a major public health concern worldwide. Until recently, no effective therapy is available to specifically inactivate the rotavirion particles within the gut. Passive immunotherapy by oral administration of chicken egg yolk antibody (lgY) has emerged of late as a fresh alternative strategy to control infectious diseases of the alimentary tract and has been applied in the treatment of diarrhea due to rotavirus infection. The purpose of this concise review is to evaluate evidence on the properties and performance of anti-rotavirus immunoglobulin Y (lgY) for prevention and treatment of rotavirus diarrhea in human and animal neonates. A survey of relevant anti-rotavirus IgY basic studies and clinical trials among neonatal animals (since 1994-2015) and humans (since 1982-2015) have been reviewed and briefly summarized. Our analysis of a number of rotavirus investigations involving animal and human clinical trials revealed that anti-rotavirus IgY significantly reduced the severity of clinical manifestation of diarrhea among IgY-treated subjects relative to a corresponding control or placebo group. The accumulated information as a whole depicts oral IgY to be a safe and efficacious option for treatment of rotavirus diarrhea in neonates. There is however a clear need for more randomized, placebo controlled and double-blind trials with bigger sample size to further solidify and confirm claims of efficacy and safety in controlling diarrhea caused by rotavirus infection especially among human infants with health issues such as low birth weights or compromised immunity in whom it is most needed.

 

 

Whole genomic analysis of human G12P[6] and G12P[8] rotavirus strains that have emerged in Myanmar.

ミャンマーで発生したヒトロタウイルG12P4[6]G12P[8]の全遺伝子解析

PLoS One, 2015, 10(5): e0124965, DOI:10.1371/jounal.pone.0124965; 1-24

Tomihiko Ide, et al.: Department of Viology and Parasitology, Fujita Health University School of Medicine

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0124965

G12 rotaviruses are emerging rotavirus strains causing severe diarrhea in infants and young children worldwide. However, the whole genomes of only a few G12 strains have been fully sequenced and analyzed. In this study, we sequenced and characterized the complete genomes of six G12 strains (RVA/Human-tc/MMR/A14/2011/G12P[8], RVA/Human-tc/MMR/A23/2011/G12P[6], RVA/Human-tc/MMR/A25/2011/G12P[8], RVA/Human-tc/MMR/P02/2011/G12P[8], RVA/Human-tc/MMR/P39/2011/G12P[8], and RVA/Human-tc/MMR/P43/2011/G12P[8]) detected in six stool samples from children with acute gastroenteritis in Myanmar. On whole genomic analysis, all six Myanmarese G12 strains were found to have a Wa-like genetic backbone: G12-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1 for strains A14, A25, P02, P39, and P43, and G12-P[6]-I1-R1-C1-M1-A1-N1-T1-E1-H1 for strain A23. Phylogenetic analysis showed that most genes of the six strains examined in this study were genetically related to globally circulating human G1, G3, G9, and G12 strains. Of note is that the NSP4 gene of strain A23 exhibited the closest relationship with the cognate genes of human-like bovine strains as well as human strains, suggesting the occurrence of reassortment between human and bovine strains. Furthermore, strains A14, A25, P02, P39, and P43 were very closely related to one another in all the 11 gene segments, indicating derivation of the five strains from a common origin. On the other hand, strain A23 consistently formed distinct clusters as to all the 11 gene segments, indicating a distinct origin of strain A23 from that of strains A14, A25, P02, P39, and P43. To our knowledge, this is the first report on whole genome-based characterization of G12 strains that have emerged in Myanmar. Our observations will provide important insights into the evolutionary dynamics of spreading G12 rotaviruses in Asia.

 

 

Anti-obesity activity of hen egg anti-lipase immunoglobulin yolk, a novel pancreatic lipase inhibitor

抗リパーゼ鶏卵抗体による抗リパーゼ活性:新規の膵リパーゼ阻害剤

Nutrition & Metabolism, 2013, 10:70; 1-6

Mai Hirose, et al.: Department of Applied Life Science, Faculty of Applied Biological Sciences, Gifu University

https://nutritionandmetabolism.biomedcentral.com/articles/10.1186/1743-7075-10-70

There is completely no report about both hen egg anti-lipase immunoglobulin yolk (IgY) and its anti-obesity action. Thus, we tried to isolate and characterize a novel anti-lipase immunoglobulin from hen egg yolk. Moreover, we investigated whether hen egg yolk anti-lipase IgY inhibits pancreatic lipase activity in vitro, and examined its ability to prevent obesity in a murine high fat diet-induced obesity model. We determined the inhibitory action of Anti-lipase IgY on lipase activity in vitro. We also focused our evaluation on the anti-obesity properties of Anti-lipase IgY in a murine high fat diet-induced obesity model. Anti-lipase IgY blocked porcine lipase activity with an IC50 of 0.49 μM. Supplementing the high fat diet with only 0.2% (w/w) of Anti-lipase IgY for 35 days significantly decreased the weights of intraperitoneal adipose tissues, epididymal, mesenteric, retroperitoneal and perirenal adipose tissues, and the amounts of hepatic total lipid, triglyceride, and cholesterol. This was accompanied by a significant increase in the fecal excretion of triglyceride in the absence of diarrhea. Furthermore, Anti-lipase IgY treatment restored body weight gain to levels similar to mice fed with Control IgY. This study provides the first report of the development of anti-lipase IgY and the direct evidence that inhibition of pancreatic lipase using Anti-lipase IgY is an effective anti-obesity treatment due to the associated increase in fecal excretion of triglyceride.

 

 

Oral passive IgY-based immunotherapeutics: A novel solution for prevention and treatment of alimentary tract diseases

経口受動免疫療法:消化管疾患の予防および治療の新しい解決策

Human Vaccines & Immunotherapeutics, 2013, 95; 1039-1048

Shofiqur Rahman, et. al.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3899138

This commentary summarizes the laboratory investigations and clinical trials published recently involving per-oral application of IgY supplemented food for specific orogastrointestinal disease prevention and control purposes. The prolonged use and misuse of conventional antibacterial drugs has spawned antibiotic resistant microbes prompting scientists to search for other germ-killing options. In particular, the use of IgY as a novel mode of immunotherapy using oral chicken immunoglobulin (IgY) to confer passive immunity has gained much interest as an inexpensive non-antibiotic alternative for the prophylaxis and treatment of a wide variety of infectious diseases. The stability of IgY in the orogastrointestinal tract and its safety profile has been well-documented. IgY has been used in the treatment or prevention of dental caries, periodontitis and gingivitis, gastritis and gastric ulcer, oral thrush and infant rotavirus diarrhea. The recent clinical trials on IgY with encouraging results has catapulted into the market novel nutraceutical or health supplements for therapeutic or prophylactic intervention based on the consumption of mono-specific or mixed IgY formulations. With recent trends in consumer preference for natural materials to alleviate health concerns, the increasing healthcare costs and the recent advances in drug delivery systems, IgY is likely to shift from its mainly functional food status toward pharmaceuticalization in the foreseeable future.

 

 

機能性卵黄リベチン(Immunoglobulin YolkIgY)の小児ロタウイルス下痢症対策の研究()

A study of pediatric rotavirus diarrhea control of functional egg yolk livetin (Immunoglobulin Yolk: IgY).

Food Style 21, 2013, 17(6); 51-53

梅田浩二ら

https://www.foodchemicalnews.co.jp/item/cartfs21/777.html 雑誌

ロタウイルス下痢症(胃腸炎)は、生後6カ月~2歳の乳幼児で多発し、重症例の25%は2歳未満の小児である。また4~ 5歳位までにほぼ全ての小児がロタウイルスに感染する。発展途上国を中心に年間約50万人の小児が下痢症で死亡しており、その内約40%はロタウイルス感染症による。2層の蛋白質の殻に覆われた2本鎖RNAのロタウイルスは、感染力が非常に強く小腸吸収上皮細胞内で増殖して、電解質・糖(延いては水)の吸収障害等による高浸透圧性下痢を引き起こす。治療はORS(経口補水塩)の経口補水療法および点滴治療による水分補給と、抗生物質およびプロバイオティクス投与の2次感染予防と整腸作用による早期回復目的の療法が行われる。一方、ロタウイルス下痢症の予防として生ワクチンが100カ国以上で認可され、多くの国で接種されているが、課題点も残されているのが現状である。紹介する機能性卵黄リベチンは、粉ミルクなどの食品および、ORS等に溶解して摂取することで消化管内にてロタウイルスを中和して感染予防およぴ発症時の早期回復に役立つ機能性食品原科である。その作用機序と効果は、第46回日米医学協力委員会ウイルス性疾患専門部会にて発表と今後の展望を提案し称賛していただいた。

 

 

In vitro cytoprotective effect of infant milk formula fortified with human Rotavirus-specific hyperimmune yolk immunoglobulins (IgY)

特異的ロタウイルス免疫卵黄グロブリンを添加した乳幼児用ミルクのIn vitroにおける細胞保護効果

Food Science and Biotechnology, 2013, 22(6); 1699-1705

Shofiqur Rahman, et al.

http://link.springer.com/article/10.1007/s10068-013-0269-4

Infant formula supplemented with hyperimmune immunoglobulin Y (IgY) against human rotavirus (HRV) was evaluated in vitro against HRV reassortant clinical strains ATCC VR 2273 and ATCC VR 2274. Specific antihuman rotavirus antibody powder (Rotamix IgY) was prepared. The effectiveness of Rotamix IgY alone and as a pre-mixed solution with infant formula was evaluated for neutralizing rotavirus infectivity in MA104 cells. The test infant formula cross-reacted strongly against different human rotavirus strains with titers of 80-320 using a 50% fluorescent focus (FF) inhibition test. Both rotamix IgY alone and in a pre-mixed solution with infant formula showed multi-serotypic cross neutralization activities against the major rotavirus global serotypes G1, G2, G3, and G4 alone and with other human and animal-strains in vitro. Cell-rotavirus adhesion and cell damage arising from rotavirus infection were significantly inhibited in a dose dependent manner, compared to control IgY supplemented infant formula.

 

 

Randomized placebo-controlled clinical trial of immunoglobulin Y as adjunct to standard supportuve therapy for rotavirus-associated diarrhea among pediatric patients

小児のロタウイルス性下痢症の標準的対症的療法における無作為的にイムノグロブリンYを添加した臨床試験

Vaccine, 2012, 30; 4661-4669

Shofiqur Rahman, et al.

http://www.sciencedirect.com/science/article/pii/S0264410X12006378

This study aims to evaluate the effect of hyperimmune immunoglobulin Y (IgY) against human rotavirus (HRV) among pediatric patients receiving standard supportive treatment for rotavirus-associated diarrhea mostly with an enteric non-cholera co-pathogen in a hospital setting. Two natural HRV reassortant clinical strains ATCC VR 2273 and ATCC VR 2274 were used as mixed immunizing antigens in poultry hens to generate anti-HRV IgY (Rota-mix IgY). The Rota-mix IgY was used in laboratory and clinical studies against control or placebo IgY. The control or placebo IgY was prepared using tissue culture medium from mock-infected MA104 cell line as antigen for poultry immunization. In vitro, Rota-mix IgY exhibited multi-serotypic cross neutralization activities along with synergistic effects against major global serotypes G1, G2, G3, G4 and other human or animal rotavirus strains when compared with mono-specific IgY. Suckling mice (ICR strain) pre-treated orally once with Rota-mix IgY and then challenged with rotavirus 3 h later showed a significant dose-dependent reduction in frequency (p < 0.05) and duration (p < 0.05) of diarrhea compared to placebo IgY-treated mice. Out of 114 children aged between 3 and 14 months and with diarrhea upon admission in a Myanmar hospital, 54 dehydrated and rotavirus-positive children were randomized into Rota-mix IgY group and placebo IgY group. Of these, only 52 children had complete data with n = 26 children per study group. Ninety-two percent of patients in each of these groups were positive for co-infecting enteric non-cholera pathogen and all patients received standard supportive therapy for diarrhea. The patients were monitored for volume and duration of oral rehydration fluid (ORF) and intravenous fluid (IVF) intake, daily stool frequency and overall duration of diarrhea, and frequency and duration of rotavirus shedding. Compared to placebo IgY group, the Rota-mix IgY group had statistically significant reduction in mean ORF intake (p = 0.004), mean duration of intravenous fluid administration (p = 0.03), mean duration of diarrhea from day of admission (p < 0.01) and mean duration of rotavirus clearance from stool from day of admission (p = 0.05). Overall, our novel approach using oral Rota-mix IgY for rotavirus-infected children mostly with non-cholera enteric pathogen co-infection appears to be a promising, safe and effective adjunct to management of acute diarrhea in pediatric patients.

 

 

Recombinant Shiga toxin B subunit can induce neutralizing immunoglobulin Y antibody

組み換え型志賀毒素Bサブユニットによる抗志賀毒素抗体の誘導

Biological & Pharmaceutical Bulletin 2012, 35 (6); 917-923

Paola Neri, et al.: Microbiology, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University

https://www.jstage.jst.go.jp/article/bpb/35/6/35_b12-00008/_article

https://www.jstage.jst.go.jp/article/bpb/35/6/35_b12-00008/_pdf

Previously, we have shown that chickens immunized with Shiga toxin (Stx) produce Stx-neutralizing egg yolk immunoglobulin Y (IgY) antibody. The anti-Stx-1 IgY and anti-Stx-2 IgY exert their neutralizing activity through their antibody activity against the B subunit of the toxin but not the A subunit. In the present study, chickens were immunized with recombinant Stx-1 B subunit (rStx-1B) and recombinant Stx-2 B subunit (rStx-2B). Induced anti-rStx-1B and anti-rStx-2B IgY neutralized the toxicity of Stx-1 and Stx-2 against HeLa 229 cells. The neutralizing activity of anti-rStx-1B IgY on Stx-1 was almost 10 times stronger than that of anti-Stx-1 IgY, and that of anti-rStx-2B IgY was 2.6 times stronger than that of anti-Stx-2 IgY. Anti-rStx-1B and anti-rStx-2B IgY reacted with multimeric and monomeric forms of the B subunits in contrast to anti-Stx-1 and anti-Stx-2 IgY that reacted with only the multimeric form. These results indicated that recombinant B subunits were promising antigens for induction of neutralizing antibodies in chickens.

 

 

Specific egg yolk immunoglobulin as a new preventive approach for Shiga-toxin mediated diseases

志賀毒素が媒介する疾病に対する新しい予防手段としての特異的卵黄イムノグロブリン

PLoS One 2011, 6(10): e26526; 1-12

Paola Neri, et al.: Microbiology, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0026526

Shiga toxins (Stxs) are involved in the development of severe systemic complications associated with enterohemorrhagic Escherichia coli (EHEC) infection. Various neutralizing agents against Stxs are under investigation for management of EHEC infection. In this study, we immunized chickens with formalin-inactivated Stx-1 or Stx-2, and obtained immunoglobulin Y (IgY) from the egg yolk. Anti-Stx-1 IgY and anti-Stx-2 IgY recognized the corresponding Stx A subunit and polymeric but not monomeric B subunit. Anti-Stx-1 IgY and anti-Stx-2 IgY suppressed the cytotoxicity of Stx-1 and Stx-2 to HeLa 229 cells, without cross-suppressive activity. The suppressive activity of these IgY was abrogated by pre-incubation with the corresponding recombinant B subunit, which suggests that the antibodies directed to the polymeric B subunits were predominantly involved in the suppression. In vivo, the intraperitoneal or intravenous administration of these IgY rescued mice from death caused by intraperitoneal injection of the corresponding toxin at a lethal dose. Moreover, oral administration of anti-Stx-2 IgY reduced the mortality of mice infected intestinally with EHEC O157:H7. Our results therefore suggest that anti-Stx IgY antibodies may be considered as preventive agents for Stx-mediated diseases in EHEC infection.

 

 

プロバイオティクスと卵黄抗体併用のピロリ菌抑制効果について ()

About the effect of suppressing Helicobacter pylori in combination with probiotics and egg yolk antibody.

臨床と研究, 2011, 88(10); 123-127

古賀泰裕ら:東海大学 医学部 感染症研究室

https://mol.medicalonline.jp/archive/search?jo=am3daidc&ye=2011&vo=88&nu=10 雑誌

1982年,オーストラリアのWarrenMarshallにより慢性胃炎患者の胃粘膜からピロリ菌(Helicobacter pylori)が発見された。その後の研究によりピロリ菌は世界の人口の半分に感染しており,胃十二指腸潰瘍および胃癌発症の主要な原因となる病原菌であることがわかった。さらに特発性血小板減少症などの胃十二指腸以外の疾病にも深く関与していることが明らかになっている。ピロリ菌除菌は,これらの胃十二指腸疾患の発症あるいは再発のリスクを下げるうえで大きな効果がある。さらに2009年,日本ヘリコバクター学会より発表された「H. pylori感染の診断と治療のガイドライン2009改訂版」では,胃十二指腸潰瘍,萎縮性胃炎,機能性デイスペプシア,特発性血小板減少症を伴うH.pylori感染症は,レベル1という明確なエビデンスが証明されており,推奨グレード分類A強い科学的根拠があり除菌を行うよう強く勧められる”に指定されている。現在,ピロリ菌の一次除菌療法とされるのがクラリスロマイシン(CAM)+アモキシシリン(AMPC)+プロトンポンプ阻害剤(PPI) 3剤の7日間投与である。一方,国内でのCAMに対する耐性ピロリ菌の増加は著しく,最近では耐性率が20%を越えるまでになり,この結果,除菌成功率は当初の90%以上から70%台にまで低下している。従ってCAMをメトロニダゾール(MNZ)に変えたレシピが二次除菌療法とされ,一次除菌療法の失敗例では保険適用となっている。しかしMNZは開発途上国では耐性化が顕著で,分離されたピロリ菌株の多くがMNZ耐性である。日本でもMNZの使用が増せば,早晩,MNZ耐性ピロリ菌が急増すると予想される。一方,多くのピロリ菌感染者はこれら上部消化管疾患をまだ未発症のいわゆる健康なピロリ菌保菌者である。これらの人々には組織学的胃炎はあるものの,臨床的に特に問題となる病変は生じていない。しかし,これらピロリ菌保菌者も非保菌者に比べれば消化性潰瘍および胃癌発症のリスクは明らかに高く,除菌を含めた何らかの対処をすべきであるが,対象者が全国で数千万人と膨大な数にのぼるため全員に抗生物質除菌を実施するのは困難である。従って抗生物質にかわるもの,たとえばプロバイオティクス(Pb)が検討されるべきである。Pbとは,口腔内から肛門に至る広義の消化管に存在する常在細菌群に働きかけて,あるいは単独で,生体に有益な効果をもたらす生きた細菌のことを指す用語である。一般にPbは消化管粘膜に分布することで病原菌が粘膜に付着することを物理的に阻害し,かつ乳酸,酢酸などを分泌することでそれらの有害菌の増殖を阻止あるいは死滅させる。ピロリ菌抑制に働くPbは胃酸に対する耐性を持つ事で強酸性の胃に生きてとどまることで,有効なピロリ茜抑制効果を発揮すると予想される。この考えに基づいて乳酸枠菌株のスクリニーングから選出されたのが,高い胃酸耐性を持つLG752(Lactobacillus gasseri GL-752)である。これまでPb単独使用によるピロリ菌抑制についての各国での臨床試験では筆者らのものも含め,多くが胃粘膜炎症の軽減および胃内定住ピロリ菌数減少を報告しているが,抗生物質を含む三剤使用による除菌療法のような完全除菌を得るのは困難であった。一方,先に述べたように,近年,耐性菌の増加のため除菌療法の成功率が低下しているが,これにPbを併用することで除菌率の有意な改善が得られている叫我々は,抗生物質多用による耐性化の広がりを防ぎかつ医療資源に頼らずに,集団におけるピロリ菌コントロールを行うために,現行のPbに抗ピロリ菌効果を有する食品成分を併用することでピロリ菌抑制を強化する方策を検討した。ピロリ菌体表面に発現するウレアーゼ(urease)は,胃内腔のウレア(urea)を分解してアンモニアを作ることで周囲胃液の酸を中和しピロリ菌の生存を維持する。また,ウレアーゼはピロリ菌の胃粘膜の接着にも関与することが報告されている叫このウレアーゼを免疫したニワトリの卵黄から精製された抗体は,抗ウレアーゼIgYと呼ばれ,ヒ卜臨床試験において尿素呼気試験で有意なピロリ菌抑制効果が得られている。今回の臨床試験では,ピロリ菌感染ボランティアを用いて,抗ピロリ菌PbであるLG752株と抗ウレアーゼIgYとを併用した場合のピロリ菌抑制効果について検討した。

 

 

Passive Oral Immunization by Egg Yolk Immunoglobulin (IgY) to Vibrio cholerae effectively Prevents Cholera

ビブリオ・コレラ菌に対する卵黄イムノグロブリン(IgY)による経口受動免疫の予防効果

Acta Medica Okayama, 2010, 64(3); 163-170

Kazuyuki Hirai, et al.: Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

http://ousar.lib.okayama-u.ac.jp/ja/40008

http://ousar.lib.okayama-u.ac.jp/files/public/4/40008/20160528034250129146/fulltext.pdf

In an attempt to prepare egg yolk immunoglobulin (IgY) to treat and prevent cholera, hens were immunized by a mixture of heat- or formalin-killed Vibrio cholerae O1 and O139 organisms, or by the recombinant cholera toxin B subunit (CTB). The IgYs were partially purified from egg yolk and orally administered to suckling mice before or after challenge with live O1 or O139 cells. The anti-O1 and O139 IgYs and the mixture of either IgY with anti-CTB IgY significantly protected the occurrence of cholera caused by both O1 and O139 infection. Since large amounts of IgY can be prepared very easily and at low cost, this seems to be a useful procedure for preventing and treating cholera.

 

 

生物から作り出される新たな医療(生物工場): たまごでピロリ菌を撃退: 抗ピロリ菌urease鶏卵抗体の開発と食品への応用 ()

New medical treatment created from living things (Biological factory): Repel Helicobacter pylori with eggs: Development of anti-Helicobacter pylori urease chicken egg antibody and application to food.

Biophilia 5, 2006, 2(1); 15-19

湯淺貴恵ら:ファーマフーズ

ここで紹介する素材は、たまご(鶏卵)というとても身近で安全な食品から作られるものだ。硬い殻に包まれた小さなたまご’'21日間、温めるとそこからヒョコという生命が誕生する。たまごは、生命を誕生させるに十分な栄養素や免疫成分が詰まっている‘‘バイオカプセルなのだ。我々はこのバイオカプセルの中でも免疫成分の1つである抗体に着目した。

 

 

鶏卵の科学とその利用:鶏卵卵黄抗体(IgY)と感染症予防 ()

Egg science and its useEgg yolk antibody (IgY) and infectious disease prevention:{Oral passive immunization by chicken egg yolk antibodies against urease of Helicobacter pylori and cell-associated glucosyltransferase of Streptococcus mutans

Food & Food Ingredients Journal of Japan, 2006, 211(11); 939-947

児玉義勝

http://sc.chat-shuffle.net/paper/uid:40015207462 雑誌検索

生まれた仔プタや仔ウシが初乳を介して母体が持っている抗体(IgG)を大量に摂取することにより、 口腔から侵入する病原体から身を守るという仕組みがある。しかし母乳を持たないトリでは、卵の卵黄が家畜の初乳に相当し、そこに親鳥からのIgGが卵黄抗体(IgY)として蓄積される。ヒナは卵黄からIgYを吸収した状態でふ化するため、ふ化後のヒナはその抗体で病原体から を守るのである。この鳥類に特徴的なIgYの母子間移行システムをバイオ工場として利用することが出来る。IgYの有用性について、ヒトに惑染し胃炎・胃沿瘍を引き起こすといわれているピロリ菌の例を挙げる。親鳥に、ピロリ菌が胃内定着に関与する菌体外膜タンパク(抗原)を数回注射すると、親鳥体内で抗原に対する特異的な抗体が作られ、それがlgYとして卵黄に移行し、蓄積する。このIgYをビロリ菌保有者が摂取すると、ピロリ菌の外膜タンパクにlgYが特異的に結合することによって定着が阻害される。このような仕組みと効果を経口受動免疫という。lgYの特徴とメリットは、1羽の親屈は1年問に約300個の卵を生むため、その卵黄から効率よくlgYが回収できる。哺乳類のlgGと比較して、IgYは抗原抗体結合力(アフィニティー)が約10倍強い。鶏病予防の目的で、連綺的なワクチネーションの方法が確立している。大羽数飼育技術が確立している。食品としての液卵ならびに粉卵の生産方法はすでに工業化されている。抗原の種類を変えるだけで、特異性の異なるlgYを一本の生産ラインで製造できる。が挙げられる。消化管粘膜をターゲットとしたユニークな特徴を有するlgYを利用した経口受動免疫療法はlgY含有食品を摂取することによって、う蝕、歯周炎、アレルギー、肥満、ピロリ菌による胃炎、原因不明な炎症性疾患などの問題を改善できると考えられる。本稿では、IgYによるピロリ菌の接着阻害とミュータンス菌のグルカン合成抑制について述べる。

Chicken egg yolk antibody possesses several merits over other antibodies due to its more specific immuno-reactivity i.e. less cross reactivity with mammalian proteins, being inexpensive, and its continuous and most humane way of producing enormous amounts without sacrificing the chicken. A chicken usually lays about 280 eggs in a year, and egg yolk contains 100-150 mg of lgY per yolk, suggesting that more than 40 g of lgY per year can be obtained from each chicken through eggs. Passive immunization by oral administration of specific antibodies has been an attractive approach against a variety of pathogens in both humans and animals. Helicobacter pylori (H. pylori) is known to be a major pathogenic factor in the development of gastritis, peptic ulcer diseases and gastric cancer in humans. H. pylori adheres and colonizes the surface of gastric mucosa using the functions of its urease. Egg yolk antibody developed against urease efficiently blocked the binding site of H. pylori to its specific mucin receptor in the gastric mucosa. So, oral administration of urease-specific lgY not only inhibited disease activity but also prevent de novo colonization in gastric mucosa, in those sites not yet infected. These encouraging results may pave the way for a novel therapeutic and prophylactic approach in the management of H. pylori-associated gastroduodenal disease. Streptococcus mutans plays an important role in the development of dental caries in humans. Major virulence factor cell-associated Glucosyltransferase (CA-GTase) degrades sucrose to form insoluble glucan, which serves as a bridge for the bacterium to bind tightly to the tooth surface. After binding of S.mutans, it release large amount of acids by fermenting a variety of sugars from the diet, which decalcify enamel, thus causing tooth decay or dental caries. Chicken anti-CA-GTase antibody effectively blocks the CA-GTase from binding to the tooth surfaces, thus inhibiting its growth and preventing the development of dental caries. Anti-CA-GTase antibody also inhibits the synthesis of insoluble glucan by the enzyme, thus assisting with the elimination of the bacterium from the oral cavity. Additionally, the use of specific antibodies (lgY) in controlling other oral microflora e.g. Porphyromonas gingivalis and Candida albicans are also taken into consideration because recent developments indicate a promising future.

 

 

Helicobacter pyloriウレアーゼ免疫グロブリンの有用性(和)

Usefulness of anti-Helicobacter pylori urease immunoglobulin.

Helicobacter Research, 2006, 10(4); 48-54

鈴木秀和ら:慶応大学医学部消化器内科

細菌感染の重要な第1段階は,局所へ菌の定着である。生体は抗原に特異的な抗体を産生することで,病原体を緋除する。この抗体を中心とした生体防御には,能動免疫と受動免疫がある。自然感染やワクチンによって成立するのが能動免疫であり,これに対して母乳に含まれている抗体など,すでに形成された抗体が別の個体に移入されるのが受動免疫である。この抗体食品の抗体源として卵黄抗体が注目されており,最近,Helicobacter pylori (H.pylori)の菌体外膜に局在するウレアーゼを抗原として精製した抗H.pyloriウレアーゼlgY が開発された。本抗体は,食品として摂取可能であり,抗生物質とは異なる面から,H.pyloriを標的とするものとして注目されている。

 

 

Effect of dietary anti-urease immunoglobulin Y on Helicobacter pylori infection in Mongolian gerbils

スナネズミを用いたピロリ菌感染における抗ウレアーゼイムノグロブリンY含有食餌の効果

HELICOBACTER, 2005, 10(1); 43-52

Sachiko Nomura, et al.: Center for Integrated Medical Research, Keio University School of Medicine

http://onlinelibrary.wiley.com/doi/10.1111/j.1523-5378.2005.00290.x/full

Helicobacter pylori is known to be a major pathogenic factor in the development of gastritis, peptic ulcer disease and gastric cancer. Recently, chicken egg yolk immunoglobulin Y (IgY) has been recognized as an inexpensive antibody source for passive immunization against gastrointestinal infections. The present study was designed to investigate the effect of anti-urease IgY on H. pylori infection in Mongolian gerbils. H. pylori-infected Mongolian gerbils were administered a diet containing anti-urease IgY, with or without famotidine (F). After 10 weeks, bacterial culture and measurement of the gastric mucosal myeloperoxidase (MPO) activity were performed. In a second experiment, another group of gerbils was started on a diet containing F + IgY a week prior to H. pylori inoculation. After 9 weeks, these animals were examined. In the H. pylori-infected gerbils, there were no significant differences in the level of H. pylori colonization among the different dietary and control groups. However, the MPO activity was significantly decreased in the H. pylori group administered the F + IgY diet compared with that in the H. pylori group administered the IgY, F, or control diet. Furthermore, in the gerbils administered the F + IgY diet prior to the bacterial inoculation, inhibition of H. pylori colonization and suppression of the elevated gastric mucosal MPO activity were observed. Oral administration of urease-specific IgY not only inhibited H. pylori disease activity in H. pylori-infected gerbils, but also prevented H. pylori colonization in those not yet infected. These encouraging results may pave the way for a novel therapeutic and prophylactic approach in the management of H. pylori-associated gastroduodenal disease.

 

 

Effect of dietary anti-Helicobacter pylori-urease immunoglobuline Y on Helicobacter pylori infection

ピロリ菌感染における抗ピロリ菌ウレアーゼ イムノグロブリンY含有食の効果

Aliment Pharmacol Ther, 2004, 20(1); 185-192

H Suzuki, et al.: Department of Internal Medicine, Keio University School of Medicine

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2036.2004.02027.x/full

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2036.2004.02027.x/epdf

Recently, chicken egg yolk was recognized as an inexpensive antibody source, and the therapeutic usefulness of egg yolk immunoglobulin Y (IgY) in oral passive immunization has been investigated. Although multiple antibiotic treatments eradicate most Helicobacter pylori (H.pylori) infections, therapy fails in 10–15% of cases due to the development of drug resistance. Consequently, it is important that new, more broadly based therapies for the treatment of H.pylori infection should be identified. The present study evaluated the effect, on H.pylori infection, of IgY prepared from egg yolk of hens immunized with H.pylori urease (anti-HpU IgY). Seventeen asymptomatic volunteers diagnosed as H.pylori-positive by the 13C-urea breath test (UBT) were orally administered anti-HpU IgY for 4 weeks. Four weeks later, UBT values were significantly decreased although no case showed H.pylori eradication. An H.pylori-positive 53-year-old female gastritis patient administered anti-HpU IgY plus lansoprazole for 8 weeks showed a decrease in serum pepsinogen (PG) I and UBT values as well as an increase in the PG I/II ratio. In conclusion, anti-HpU IgY may mitigate H.pylori-associated gastritis and partially attenuate gastric urease activity. Furthermore, anti-HpU IgY combined with antacids appears to ameliorate gastric inflammation. These encouraging results may represent a novel approach to the management of H.pylori-associated gastroduodenal disease.

 

 

Suppressive effect of functional drinking yogurt containing specific egg yolk immunoglobulin on Helicobacter pylori in humans

ヒトにおけるピロリ菌に対する特異卵黄イムノグロブリン含有機能性ドリンクヨーグルトの抑制効果

Journal of Dairy Science, 2004, 87(12); 4073-4079

K Horie, at al.: Research Department, Pharma Foods

http://www.journalofdairyscience.org/article/S0022-0302(04)73549-3/abstract

http://www.journalofdairyscience.org/article/S0022-0302(04)73549-3/pdf

Helicobacter pylori is a human pathogen that infects over 50% of the population worldwide. It is the most important etiologic agent of gastroduodenal ulcers and malignancies. Helicobacter pylori urease enzyme is considered the main factor for the organism's colonization in the gastroduodenal mucosa. Hens immunized with the purified urease produce a highly specific anti-H. pylori urease immunoglobulin (IgY-urease) in their egg yolks. Immunoglobulin Y-urease was stable at 60 to 65°C for 30 min and at pH 4.0 for 7 h. Its activity was lost at 80°C for 20 min and at pH 2 for 4 h. Specially designed functional drinking yogurt containing Lactobacillus acidophilus and Bifidobacterium spp. with 1% egg yolk IgY-urease was produced commercially. Immunoglobulin Y-urease activity showed stability in the product up to 7 d, and then decreased to 85% after 3 wk of storage. A clinical study was conducted to determine the effectiveness of IgY-urease yogurt to suppress infection in humans. Forty-two volunteers who tested positive for H. pylori using a 13C-urea breath test were recruited. A total of 450 mL of IgY-urease (test group) or IgY-urease–free yogurt (control group) was consumed in 150-mL portions 3 times daily for 4 wk. Volunteers were tested after 2 and 4 wk; urea breath test values significantly decreased in the test group compared with the control group. The results indicate that suppression of H. pylori infection in humans could be achieved by consumption of drinking yogurt fortified with IgY-urease.

 

 

抗ピロリ菌鶏卵抗体(IgY)の開発と食品への応用 ()

Development of anti-Helicobacter pylori urease IgY and its application for food product

食品と開発, 2003, 38(11); 70-72

山根哲郎ら:松下記念病院

https://jglobal.jst.go.jp/detail?JGLOBAL_ID=200902224560818073 雑誌検索

ヘリコバクター・ピロリ菌(以下ピロリ菌とする)は、1982年にオーストラリアのMarshallWarrenによって胃の組織から発見されたグラム陰性の桿菌である。らせん状の形態をした微好気性菌であり、数本の有鞘鞭毛を持ちその形態的特徴からヘリコプターのヘリコと同じ意味でHelicobacterと名付けられた1)。極めて強いウレアーゼ活性を有し、胃粘液中の尿素を分解することでアンモニアを産生し、胃酸を中和しており、このシステムによりピロリ菌は強酸性の胃内でも生育することができると考えられている。その後、この菌と胃疾患との関連性が注目され世界中で研究が進められている。日本国内における感染率は、40歳代以上で約80%と報告されており、先進国の中では非常に高い感染率を示している。本菌は、消化器疾患患者だけでなく、健常人からも検出され、感染者の全てが消化器疾患を発症するとは限らない。しかし、ビロリ菌は、胃炎または胃潰瘍患者の約90%が感染しており、除菌治療を行うことで潰瘍が治癒することが確認されている。このことによりピロリ菌が消化器疾患における重要な危険因子であることは明らかである。日本国内においても、消化器系疾患の治療には先ずピロリ菌の除菌が必要であるとの指針が厚生労働省から出されており、抗生物質と胃酸分泌抑制剤を組み合わせた2~3剤併用療法が行われている。

Helicobacter pylori (hereafter abbreviated as H.pylori) is a gram-negative rod, which was discovered from the stomach tissue by Marshall and Warren, Australians, in 1982. This is a microaerophilic bacterium with a helical shape and has several flagella. The name of Helicobacter was derived from the word "helicopter" based on its morphological characteristics. H.pylori has very strong urease activity, producing ammonia by degrading urea in the gastric mucosa, which neutralizes gastric acid. It has been considered that such system enables H.pylori to grow even in the stomach with its very strong acidity. Since then, the relevance of H.pylori to gastropathy has received great attention and has been studied throughout the world. The rate of H.pylori infection in Japan has been reponed to be about 80% in people at 40 years or more of age, which is very high in the developed countries. H.pylori is detected in the healthy people as well as in the patients with the digestive diseases, indicating that all persons infected with H.pylori do not necessarily suffer from the digestive diseases. About 90% of patients with gastritis or gastric ulcer are, however, infected with H.pylori, and it has been confirmed that gastric ulcer can be cured by the H.pylori eradication therapy. From this fact, it is obvious that H.pylori is a crucial risk factor in the occurrence of the digestive diseases. In Japan, the Ministry of Health, Labor and Welfare issued the guideline thar the H.pylori eradication is the first thing that must be done in treating digestive system diseases and the combination therapy of 2 or 3 drugs including antibiotics and inhibitors of gastric secretion, is being administrated.

 

 

Helicobacter pyloriウレアーゼ卵黄抗体(和)

Anti-Helicobacter pylori urease egg yolk antibody

Helicobacter Research, 2002, 6(2); 35-39

谷典子ら:ファーマフーズ

現在までにHelicobacter pylori (H. pylori)と消化器系疾患との関連性が明らかになってきており,胃・十二指腸潰瘍など消化器系疾患の治療の際,H.pyloriを除菌することで再発率が低下することが報告されている。除菌方法としては,抗菌薬と胃酸分泌抑制薬などを組み合わせた多剤併用療法がおこなわれているが,副作用,耐性菌の問題も指摘されており,安全で負担の少ない新しい除菌方法の開発が望まれている。一方,最近では食品成分による除菌方法も種々検討されており,なかでも抗H.pyloriウレアーゼ卵黄抗体は,鳥類がもつ特徴的な免疫システムを利用して得られた免疫食品成分であり,H.pyloriウレアーゼにのみ特巽的に作用する卵由来の蛋白質(抗体)である。安全でしかも除菌効果が期待されているまったく新しいタイプの食品素材である。

 

 

1章 新しいプロバイオ食品が台頭。次のヒット商品はこれだ!: 添加型の機能性ヨーグルト (韓国ドリンクヨーグルト「gut)()

Chapter 1 Rise of new professional bio foods. This is the next hit product! : Additive-type functional yogurt (Korean drink yogurt "gut")

日経バイオビジネス, 2002, (7); 66-68

日経バイオビジネス編集部

韓国のメール社(ソウル市)が販売する「gut」は、胃のピロリ菌を除去するドリンクヨーグルト。しかし機能を発揮しているのは乳酸菌ではなく、鶏卵から製造した抗ピロリ菌抗体だ。機能性ヨーグルトの進化の1つの方向は、このようにヨーグルトの機能を、機能性食材のキャリア(担体)と割り切って使う方向に傾いている。それはヨーグルトに、キャリアとしての重要な資質があるからだ。例えばおいしくて栄養価が高いこと、半固形なので溶けにくい機能性成分も添加しやすいこと、保存期間中の劣化問題が少ないこと(保存期間が短いため)、毎日食べる習慣にしやすいこと、そして消費者の元までチルドで流通することなどだ。特に、比較的不安定なたんぱく質の機能を食品で発揮させようとするときには、チルドで流通するという利点は重要といえるだろう。さて、「gut」の鶏卵抗体原末を製造しているのは日本で種鶏の輸入販売、孵化事業を行っているゲン・コーポレーションだ。抗体製造には、「母子免疫」の仕組みを利用している。新生したばかりの動物は免疫抗体を持っていない。そのため哺乳動物では初乳を介して母親の免疫抗体が子供に受け渡される。鶏の場合、初乳の役割を卵黄の一部が担っているため、卵の中に親鶏の免疫抗体が受け渡される。この仕組みを利用し、ピロリ菌が胃に接着するためのたんばく質で免疫した鶏に抗体入りの卵を生ませる。ノウハウが必要だが抗体製造の原理は単純。原末の価格は比較的安価なようで、韓国で「gut」は、100円ほどの価格で販売されているようだ。ゲン・コーポレーションが販売する抗体の原末は日本ではまだ健康食品に使われているだけだ。抗体入りのヨーグルトは発売されていないが、同社は「日本でもぜひ、抗体入りヨーグルトを商品化してもらいたい」と、抗体原末の営業に力をいれている。まだ具体的な話には至っていないが、複数の乳業会社と鶏卵抗体入りドリンクヨーグルトの商品化で話し合いを進めているという。

 

 

Adherence Protects the Binding Sites of Helicobacter pylori Urease from Acid-Induced Damage

付着がピロリ菌ウレアーゼの結合部位を酸によるダメージから保護する

Microbiology and Immunology, 2000, 44(9); 773-776

Faustino C. Icatlo, et al.

http://www.ingentaconnect.com/content/bpl/mim/2000/00000044/00000009/art00006;jsessionid=35l75g5j699ac.alice

Colonization by Helicobacter pylori partly depends on aciddependent adherence by urease to gastric mucin. To further verify the relevance of urease adherence to colonization, the influence of acidity on the binding sites of H. pylori urease was investigated. When enzymebased in vitro ligand capture assays were used, the effect of acidity on the binding site of H. pylori urease was determined against a backdrop medium consisting of acidic buffers simulating the luminal side of gastric mucus. A high degree of stability was exhibited by adherent urease, suggesting a pivotal role by the denatured enzyme in the persistence of the bacterium within the acidified compartment of gastric mucus.

 

 

Enhanced reduction of Helicobacter pylori load in precolonized mice treated with combined famotidine and urease-binding polysaccharides

ファモチジンとウレアーゼ結合型多糖類を併用処理したマウスにおけるヘリコバクター・ピロリの著しい減少

Antimicrobial Agent and Chemotherapy, 2000, 44; 2492-2497

Faustino C. Icatlo, Jr., et al.

http://aac.asm.org/content/44/9/2492.abstract

http://aac.asm.org/content/44/9/2492.full.pdf

The present study investigated the effect of a model urease-binding polysaccharide in combination with a histamine H2 receptor antagonist on Helicobacter pylori colonization in vivo. Euthymic hairless mice were treated daily with dextran sulfate via drinking water and/or famotidine via intragastric gavage starting at 1 week postchallenge with a CagA+ VacA+ (type 1) strain of H.pylori. Treatment of precolonized mice for 2 weeks with dextran sulfate combined with famotidine yielded a group mean bacterial load (per 100 mg of gastric tissue) of log101.04 CFU, which was significantly lower than those of the famotidine (log10 3.35 CFU, P < 0.01) and dextran sulfate (log10 2.45 CFU, P < 0.05) monotherapy groups and the infected nontreated group (log103.64 CFU, P < 0.01). Eradication was achieved after 2 weeks of treatment in 50% or more of the test mice using drug combinations (1 or 2 weeks of famotidine plus 2 weeks of dextran sulfate) versus none in the monotherapy and positive control groups. The enhanced activity of the drug combination may be related to the daily pattern of transient acid suppression by famotidine inducing periodic bacterial convergence to superficial mucus sites penetrated by dextran sulfate from the lumen. Increased urease-dextran sulfate avidity was observed in vitro in the presence of famotidine and may partly account for the enhanced activity. With potential utility in abbreviating treatment time and eradication of antibiotic-resistant strains, the use of urease-targeted polysaccharides concurrently with a gastric acid inhibitor warrants consideration as an additional component of the standard multidrug chemotherapy of H.pylori infection.

 

 

Acid-dependent adherence of Helicobacter pylori urease to diverse polysaccharides

ヘリコバクター・ピロリ ウレアーゼの多様な多糖類への酸依存性接着

GASTROENTEROLOGY, 2000, 119; 358-367

FAUSTINO C. ICATLO, Jr, et al.

http://www.gastrojournal.org/article/S0016-5085(00)71015-8/abstract

http://www.gastrojournal.org/article/S0016-5085(00)71015-8/pdf

The significance of acid-primed recognition of ligands by Helicobacter pylori urease is unknown. This study aimed to further characterize the specificity of urease adherence in vitro and verify whether specific inhibition will translate into in vivo suppression of colonization. A highly sensitive competitive enzyme-linked ligand capture assay was used to quantify the capacity of each test inhibitor to compete with labeled mucin for binding sites on immobilized native urease. A model polymer that strongly bound urease was used in an in vivo trial using euthymic hairless mice as an infection model. The blockage of urease–gastric mucin interaction by certain inhibitors revealed an acid-functional lectin-like activity by urease, specifically recognizing bacterial lipopolysaccharides and certain species of polysaccharides, nonbacterial glycolipids, and glycoproteins. Dextran sulfate significantly (P < 0.01) suppressed colonization of mice by H. pylori when given before and/or after challenge. The acid-driven high-affinity adherence of H. pylori urease to mucin and lipopolysaccharides contributes to gastric mucosal colonization by the bacterium based on in vivo targeting experiments using specific polysaccharides in a mouse model with acute infection. Acid-functional urease-homing polysaccharides that can interfere with urease-mucin or H. pylori whole cell–mucin interaction in vitro can significantly interfere with colonization by the bacterium in vivo.

 

 

Affinity purification of Helicobacter pylori urease

ヘリコバクター・ピロリ ウレアーゼのアフィニティー精製

The Journal Biological Chemistry, 1998, 273(29); 18130-18138

Faustino C. Icatlo, Jr., et al.

http://www.jbc.org/content/273/29/18130.short

http://www.jbc.org/content/273/29/18130.full.pdf

A simple, re-producible and high yield method of Helicobacter pylori urease enzyme purification was developed using a heparinoid (Cellufine sulfate) affinity gel. The purification method involved two sequential steps using the same gel that takes advantage of the differential affinity of urease to the heparinoid at two levels of hydrogen ion concentration. SDS-polyacrylamide gel electrophoresis analysis of affinity-purified urease revealed two major protein bands with about 62- and 30-kDa molecular mass. When whole cell lysates of clinical and laboratory strains of H. pylori were probed by Western blot, anti-urease hyperimmune serum produced by affinity-purified urease in rabbit recognized only the two bands corresponding to the urease A and B subunits. To probe the molecular relevance of affinity gel adherence to mucin adherence, the purified urease was derivatized with N-hydroxysuccinimidobiotin and used in adherence assays. Competitive inhibition tests revealed commonality of urease receptors among gastric mucin, heparin, and heparinoid. Composite data on adherence kinetics modulated by pH, salt, incubation time, and concentration of urease or mucin were indicative of conformation-dependent ligand-receptor interaction.

 

 

A euthymic Hairless mouse model of Helicobacter pylori colonization and adherence to gastric epithelial cells In vivo

In vivoにおけるヘリコバクター・ピロリのヘアレスマウス胃上皮細胞への定着及び接着モデル

Clinical and Diagnostic Laboratory Immunology, 1998, 5(4); 578-582

NOBUTAKE KIMURA, et al.: Fine Chemicals Research Laboratory, Nisshin Flour Milling Co., Ltd

http://cvi.asm.org/content/5/4/578.short

http://cvi.asm.org/content/5/4/578.full.pdf+html

The hairless mouse strain NS:Hr/ICR was examined as a potential small animal model of Helicobacter pylori colonization, adherence to gastric epithelial cells in vivo, and gastritis. Among several small animals tested, NS:Hr/ICR mice proved to be the most highly susceptible to H.pylori infection. Challenge with clinical isolates of H.pylori consisting of either phenotype I or II (VacA and CagA positive and negative, respectively) resulted in colonization by mucus-resident and epithelial cell-adherent bacterial populations. Cell-adherent bacteria resisted 80 cycles of top-speed vortex washing and were recovered only by homogenization of serially washed glandular stomach tissue, indicating intimate association with the mucosal surface. Immunoperoxidase staining of paraffin sections of gastric tissue from infected mice revealed H.pylori antigens localized in the glandular region of the mucosa, with some colonized areas seen in the vicinity of submucosal mononuclear cell infiltration. The latter inflammatory reaction was observed as a function of the H.pylori phenotype (only type I induced inflammation) and the challenge dose (only those mice challenged with 108 CFU or higher showed the reaction). The NS:Hr/ICR strain of mice is a suitable miniature model of H. pylori infection and may prove useful in the quest for an efficacious mode of treatment for this common infection in humans.

 

 

Oral passive immunization against experimental salmonellosis in mice using chicken egg yolk antibodies specific for Salmonella enteritidis and S. typhimurium

サルモネラ・エンテリチジス及びサルモネラ・チフィムリウヌに対する鶏卵黄特異抗体を用いたマウス実験的サルモネラ症に対する経口受動免疫

Vaccine 1998, 16(4): 388-393

Hideaki Yokoyama, et al.

http://www.sciencedirect.com/science/article/pii/S0264410X97809164

The efficacy of chicken egg yolk homotypic antibodies specific for outer membrane proteins (OMP), lipopolysaccharide (LPS) or flagella (Fla) in controlling experimental salmonellosis in mice was investigated. Mice challenged orally with 2 × 109 c.f.u. of Salmonella enteritidis or 2 × 107 c.f.u. of S.typhimurium were orally treated with 0.2 ml anti-OMP, -LPS or -Fla yolk antibody three times a day for three consecutive days. In mice challenged with S. enteritidis, antibody treatment resulted in a survival rate of 80%, 47% and 60% using OMP, LPS or Fla specific antibodies respectively, in contrast to only 20% in control mice. In the S.typhimurium trial, survival rate was 40%, 30% and 20% using OMP, LPS or Fla specific antibodies respectively in contrast to 0% in control mice. In vitro adhesion of S.enteritidis and S.typhimurium to HeLa cells was significantly reduced by anti-OMP, -LPS, and -Fla homotypic antibodies. Results suggest that egg yolk antibodies specific for Salmonella OMP, LPS, and Fla may protect mice from experimental salmonellosis when passively administered orally. Of these antibodies, anti-OMP exhibited the highest level of protection in vivo and in vitro.

 

 

Passive immunization against experimental salmonellosis in mice by orally administered hen egg-yolk antibodies specific for 14-kDa fimbriae of Salmonella Enteritidis

サルモネラ・エンテリチジスの14キロダルドン線毛に対する鶏卵特異抗体の経口投与によるマウス実験的サルモネラ症に対する受動免疫

Journal of Medical Microbiology 1994, 41 : 29-35

R. C. PERALTA, et al.

http://jmm.microbiologyresearch.org/content/journal/jmm/10.1099/00222615-41-1-29

Chickens were immunised with a preparation of purified 14-kDa fimbriae of  serotype Enteritidis (SEF 14) to raise egg-yolk antibodies for protection trials in mice against subsequent challenge-exposure with the homologous strain of Enteritidis. A pronounced specificity of egg-yolk antibodies against the 14-kDa fimbrial antigen was demonstrated by Western blotting analysis. Passive antibody protection was evaluated in a mouse model of experimental salmonellosis: 79 mice (CD 1 strain) were challenged orally with 2 × 10 cfu of Enteritidis. Test mice treated with SEF-14 antibodies (titre = 128) had a survival rate of 77.8% compared to 32% survival in control mice fed normal egg-yolk antibodies (titre < 10) (p < 0.01). In-vitro adhesion of Enteritidis to mouse intestinal epithelial cells was reduced by anti-fimbrial antibodies. An indirect immunofluorescence method demonstrated the localisation of Enteritidis along the villous margins of the small intestine of control mice, whereas in test mice adherent bacteria were not detected. Results suggest that 14-kDa fimbriae may influence, enhance or contribute to the overall adhesive properties of Enteritidis and that egg-yolk antibodies directed against these fimbriae may have played a substantial role in protection, possibly by minimising bacterial colonisation and invasion during the early stages of infection.

 

 

Prevention of Human Rotavirus Infection with Chicken Egg Yolk Immunoglobulins Containing Rotavirus Antibody in Cat

抗ロタウイスル鶏卵黄抗体のヒトロタウイルス感染ネコにおける予防効果

Japanese Association for Infectious Diseases, 1990, 64; 118-123

Chikane HIRAGA, et al.: Department of Bacteriology, Saitama Medical School

https://www.jstage.jst.go.jp/article/kansenshogakuzasshi1970/64/1/64_1_118/_pdf

A study was made on the passive protection against rotavirus-induced diarrhea. Chickens were immunized with bovine rotavirus (serotype 1) and the egg yolk immunoglobulins containing a high titer anti-rotavirus neutralizing antibody (CEYI) was obtained. The CEYI was then orally administered to specific-pathogen-free cats, and the cats were infected with human rotavirus. The cats treated with the CEYI remained clinically healthy after challenge, whereas diarrhea occurred in the placebo-fed cats as control. Virus antigens were detected in feces in all the diarrheal cases in the placebo-fed cats but were only sporadically detected in the CEYI-fed cats. However, the cats were only protected against rotavirus infection by the presence in the gut at the time of infection of the antibody. These results suggested that continuous administration of the CEYI is capable of preventing children from diarrhea induced by human rotavirus infection and viral shedding.
                                     

Immunology Research Institute in gifu

839-7, Sano, Gifu-City,

501-1101, Japan

TEL 058-235-7303

document-request@igy-research.com