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DOI	10.1073/pnas.2018032118
	Dissecting serotype-specific contributions to live oral cholera vaccine efficacy
	Sit B.; Fakoya B.; Zhang T.; Billings G.; Waldor M.K.
发表日期	2021
ISSN	00278424
卷号	118 期号:7
英文摘要	The O1 serogroup of Vibrio cholerae causes pandemic cholera and is divided into the Ogawa and Inaba serotypes. The O-antigen is V. cholerae’s immunodominant antigen, and the two serotypes, which differ by the presence or absence of a terminally methylated O-antigen, likely influence development of immunity to cholera and oral cholera vaccines (OCVs). However, there is no consensus regarding the relative immunological potency of each serotype, in part because previous studies relied on genetically heterogeneous strains. Here, we engineered matched serotype variants of a live OCV candidate, HaitiV, and used a germfree mouse model to evaluate the immunogenicity and protective efficacy of each vaccine serotype. By combining vibriocidal antibody quantification with single- and mixed-strain infection assays, we found that all three HaitiV variants—InabaV, OgawaV, and HikoV (bivalent Inaba/Ogawa)—were immunogenic and protective. None of the vaccine serotypes were superior across both of these vaccine metrics, suggesting that the impact of O1-serotype variation in OCV design, although detectable, is subtle. However, all three live vaccines significantly outperformed formalin-killed HikoV, supporting the idea that live OCV usage will bolster current cholera control practices. The potency of OCVs was found to be challenge strain-dependent, emphasizing the importance of appropriate strain selection for cholera challenge studies. Our findings and experimental approaches will be valuable for guiding the development of live OCVs and oral vaccines for additional pathogens. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Vibrio cholerae \| live-attenuated vaccines \| germfree mice
语种	英语
scopus关键词	bacterium antibody; cholera vaccine; adult; agglutination test; animal experiment; animal model; antibody titer; Article; bacterial growth; cholera; cohort analysis; controlled study; drug design; drug efficacy; drug potency; drug use; female; genetic variability; immunogenicity; in vivo study; infant; infection control; infection prevention; male; mouse; nonhuman; priority journal; serotype; Vibrio cholerae
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180650
作者单位	Division of Infectious Diseases, Brigham and Women’s Hospital, Boston, MA 02115, United States; Department of Microbiology, Harvard Medical School, Boston, MA 02115, United States; Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA 02115, United States; Howard Hughes MedicalInstitute, Boston, MA 02115, United States
推荐引用方式 GB/T 7714	Sit B.,Fakoya B.,Zhang T.,et al. Dissecting serotype-specific contributions to live oral cholera vaccine efficacy[J],2021,118(7).
APA	Sit B.,Fakoya B.,Zhang T.,Billings G.,&Waldor M.K..(2021).Dissecting serotype-specific contributions to live oral cholera vaccine efficacy.Proceedings of the National Academy of Sciences of the United States of America,118(7).
MLA	Sit B.,et al."Dissecting serotype-specific contributions to live oral cholera vaccine efficacy".Proceedings of the National Academy of Sciences of the United States of America 118.7(2021).