Oral immunization with a probiotic cholera vaccine induces broad protective immunity against Vibrio cholerae colonization and disease in mice.

Oral cholera vaccines (OCVs) are being increasingly employed, but current killed formulations generally require multiple doses and lack efficacy in young children. We recently developed a new live-attenuated OCV candidate (HaitiV) derived from a Vibrio cholerae strain isolated during the 2010 Haiti...

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Main Authors: Brandon Sit, Ting Zhang, Bolutife Fakoya, Aklima Akter, Rajib Biswas, Edward T Ryan, Matthew K Waldor
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2019-05-01
Series:PLoS Neglected Tropical Diseases
Online Access:https://doi.org/10.1371/journal.pntd.0007417
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spelling doaj-e9ffc8d26be744d3aa6564a3a2a5b4a92021-06-23T04:30:44ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352019-05-01135e000741710.1371/journal.pntd.0007417Oral immunization with a probiotic cholera vaccine induces broad protective immunity against Vibrio cholerae colonization and disease in mice.Brandon SitTing ZhangBolutife FakoyaAklima AkterRajib BiswasEdward T RyanMatthew K WaldorOral cholera vaccines (OCVs) are being increasingly employed, but current killed formulations generally require multiple doses and lack efficacy in young children. We recently developed a new live-attenuated OCV candidate (HaitiV) derived from a Vibrio cholerae strain isolated during the 2010 Haiti cholera epidemic. HaitiV exhibited an unexpected probiotic-like activity in infant rabbits, preventing intestinal colonization and disease by wild-type V. cholerae before the onset of adaptive immunity. However, it remained unknown whether HaitiV would behave similarly to other OCVs to stimulate adaptive immunity against V. cholerae. Here, we orally immunized adult germ-free female mice to test HaitiV's immunogenicity. HaitiV safely and stably colonized vaccinated mice and induced known adaptive immune correlates of cholera protection within 14 days of administration. Pups born to immunized mice were protected against lethal challenges of both homologous and heterologous V. cholerae strains. Cross-fostering experiments revealed that protection was not dependent on vaccine colonization in or transmission to the pups. These findings demonstrate the protective immunogenicity of HaitiV and support its development as a new tool for limiting cholera.https://doi.org/10.1371/journal.pntd.0007417
collection DOAJ
language English
format Article
sources DOAJ
author Brandon Sit
Ting Zhang
Bolutife Fakoya
Aklima Akter
Rajib Biswas
Edward T Ryan
Matthew K Waldor
spellingShingle Brandon Sit
Ting Zhang
Bolutife Fakoya
Aklima Akter
Rajib Biswas
Edward T Ryan
Matthew K Waldor
Oral immunization with a probiotic cholera vaccine induces broad protective immunity against Vibrio cholerae colonization and disease in mice.
PLoS Neglected Tropical Diseases
author_facet Brandon Sit
Ting Zhang
Bolutife Fakoya
Aklima Akter
Rajib Biswas
Edward T Ryan
Matthew K Waldor
author_sort Brandon Sit
title Oral immunization with a probiotic cholera vaccine induces broad protective immunity against Vibrio cholerae colonization and disease in mice.
title_short Oral immunization with a probiotic cholera vaccine induces broad protective immunity against Vibrio cholerae colonization and disease in mice.
title_full Oral immunization with a probiotic cholera vaccine induces broad protective immunity against Vibrio cholerae colonization and disease in mice.
title_fullStr Oral immunization with a probiotic cholera vaccine induces broad protective immunity against Vibrio cholerae colonization and disease in mice.
title_full_unstemmed Oral immunization with a probiotic cholera vaccine induces broad protective immunity against Vibrio cholerae colonization and disease in mice.
title_sort oral immunization with a probiotic cholera vaccine induces broad protective immunity against vibrio cholerae colonization and disease in mice.
publisher Public Library of Science (PLoS)
series PLoS Neglected Tropical Diseases
issn 1935-2727
1935-2735
publishDate 2019-05-01
description Oral cholera vaccines (OCVs) are being increasingly employed, but current killed formulations generally require multiple doses and lack efficacy in young children. We recently developed a new live-attenuated OCV candidate (HaitiV) derived from a Vibrio cholerae strain isolated during the 2010 Haiti cholera epidemic. HaitiV exhibited an unexpected probiotic-like activity in infant rabbits, preventing intestinal colonization and disease by wild-type V. cholerae before the onset of adaptive immunity. However, it remained unknown whether HaitiV would behave similarly to other OCVs to stimulate adaptive immunity against V. cholerae. Here, we orally immunized adult germ-free female mice to test HaitiV's immunogenicity. HaitiV safely and stably colonized vaccinated mice and induced known adaptive immune correlates of cholera protection within 14 days of administration. Pups born to immunized mice were protected against lethal challenges of both homologous and heterologous V. cholerae strains. Cross-fostering experiments revealed that protection was not dependent on vaccine colonization in or transmission to the pups. These findings demonstrate the protective immunogenicity of HaitiV and support its development as a new tool for limiting cholera.
url https://doi.org/10.1371/journal.pntd.0007417
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