Dataset Information

Rice-based oral antibody fragment prophylaxis and therapy against rotavirus infection.

ABSTRACT: Rotavirus-induced diarrhea is a life-threatening disease in immunocompromised individuals and in children in developing countries. We have developed a system for prophylaxis and therapy against rotavirus disease using transgenic rice expressing the neutralizing variable domain of a rotavirus-specific llama heavy-chain antibody fragment (MucoRice-ARP1). MucoRice-ARP1 was produced at high levels in rice seeds using an overexpression system and RNAi technology to suppress the production of major rice endogenous storage proteins. Orally administered MucoRice-ARP1 markedly decreased the viral load in immunocompetent and immunodeficient mice. The antibody retained in vitro neutralizing activity after long-term storage (>1 yr) and boiling and conferred protection in mice even after heat treatment at 94°C for 30 minutes. High-yield, water-soluble, and purification-free MucoRice-ARP1 thus forms the basis for orally administered prophylaxis and therapy against rotavirus infections.

SUBMITTER: Tokuhara D

PROVIDER: S-EPMC3754275 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Rice-based oral antibody fragment prophylaxis and therapy against rotavirus infection.

Tokuhara Daisuke D Álvarez Beatriz B Mejima Mio M Hiroiwa Tomoko T Takahashi Yuko Y Kurokawa Shiho S Kuroda Masaharu M Oyama Masaaki M Kozuka-Hata Hiroko H Nochi Tomonori T Sagara Hiroshi H Aladin Farah F Marcotte Harold H Frenken Leon G J LG Iturriza-Gómara Miren M Kiyono Hiroshi H Hammarström Lennart L Yuki Yoshikazu Y

The Journal of clinical investigation 20130808 9

Rotavirus-induced diarrhea is a life-threatening disease in immunocompromised individuals and in children in developing countries. We have developed a system for prophylaxis and therapy against rotavirus disease using transgenic rice expressing the neutralizing variable domain of a rotavirus-specific llama heavy-chain antibody fragment (MucoRice-ARP1). MucoRice-ARP1 was produced at high levels in rice seeds using an overexpression system and RNAi technology to suppress the production of major ri ...[more]

PMID: 23925294

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Project description:BackgroundThe monovalent oral rotavirus vaccine Rotarix® was introduced into the UK infant immunisation programme in 2013. We estimated vaccine effectiveness (VE) in the first two years of the programme.MethodsWe used a test-negative case-control design and enhanced national surveillance data for 1869 vaccine-eligible children tested for rotavirus infection to obtain adjusted odds ratios and VE against laboratory-confirmed rotavirus infections. Linked anonymised UK primary care and hospitalisation data from the Clinical Practice Research Datalink (40,723 children) and random-effects Poisson regression were used in a cohort study to estimate VE against all-cause acute gastroenteritis (AGE) and AGE hospitalisations.ResultsVE against laboratory-confirmed infection was 69% (95% Confidence Interval: 40-84%) for one dose and 77% (95%CI: 66-85%) for two doses. Two-dose VE in children aged <12 months and ≥12 months was 85% (95%CI: 74-91%) and 54% (95%CI: 15-75%), respectively. In contrast, we found no evidence that the vaccine was effective against all-cause AGE (VE = -20%, 95%CI: -36% to -5%), or against AGE hospitalisations (VE = 35%, 95% CI: -86% to 77%).ConclusionsIn this first detailed assessment of VE of the Rotarix® vaccine in the English national programme, we show that Rotarix® was highly effective in preventing laboratory-confirmed rotavirus infection in young children. This provides reassurance about the vaccine's performance in real-life settings and gives key information for future cost-effectiveness analyses. The high VE against rotavirus-specific AGE, and the exceptionally successful implementation of the national rotavirus vaccine programme (with >90% vaccine coverage), explains the lack of VE against all-cause AGE because most AGE in the post-vaccine era would not have been due to rotavirus, although some underestimation of VE could also have occurred due to differential healthcare utilisation by vaccinated and unvaccinated infants. This highlights the importance of using specific vaccine-preventable endpoints for these scenarios.

Dataset Information

Rice-based oral antibody fragment prophylaxis and therapy against rotavirus infection.

Publications

Rice-based oral antibody fragment prophylaxis and therapy against rotavirus infection.

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