Cargando…

A hexavalent Coxsackievirus B vaccine is highly immunogenic and has a strong protective capacity in mice and nonhuman primates

Coxsackievirus B (CVB) enteroviruses are common human pathogens known to cause severe diseases including myocarditis, chronic dilated cardiomyopathy, and aseptic meningitis. CVBs are also hypothesized to be a causal factor in type 1 diabetes. Vaccines against CVBs are not currently available, and he...

Descripción completa

Detalles Bibliográficos
Autores principales: Stone, V. M., Hankaniemi, M. M., Laitinen, O. H., Sioofy-Khojine, A. B., Lin, A., Diaz Lozano, I. M., Mazur, M. A., Marjomäki, V., Loré, K., Hyöty, H., Hytönen, V. P., Flodström-Tullberg, M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202868/
https://www.ncbi.nlm.nih.gov/pubmed/32494709
http://dx.doi.org/10.1126/sciadv.aaz2433
_version_ 1783529778532319232
author Stone, V. M.
Hankaniemi, M. M.
Laitinen, O. H.
Sioofy-Khojine, A. B.
Lin, A.
Diaz Lozano, I. M.
Mazur, M. A.
Marjomäki, V.
Loré, K.
Hyöty, H.
Hytönen, V. P.
Flodström-Tullberg, M.
author_facet Stone, V. M.
Hankaniemi, M. M.
Laitinen, O. H.
Sioofy-Khojine, A. B.
Lin, A.
Diaz Lozano, I. M.
Mazur, M. A.
Marjomäki, V.
Loré, K.
Hyöty, H.
Hytönen, V. P.
Flodström-Tullberg, M.
author_sort Stone, V. M.
collection PubMed
description Coxsackievirus B (CVB) enteroviruses are common human pathogens known to cause severe diseases including myocarditis, chronic dilated cardiomyopathy, and aseptic meningitis. CVBs are also hypothesized to be a causal factor in type 1 diabetes. Vaccines against CVBs are not currently available, and here we describe the generation and preclinical testing of a novel hexavalent vaccine targeting the six known CVB serotypes. We show that the vaccine has an excellent safety profile in murine models and nonhuman primates and that it induces strong neutralizing antibody responses to the six serotypes in both species without an adjuvant. We also demonstrate that the vaccine provides immunity against acute CVB infections in mice, including CVB infections known to cause virus-induced myocarditis. In addition, it blocks CVB-induced diabetes in a genetically permissive mouse model. Our preclinical proof-of-concept studies demonstrate the successful generation of a promising hexavalent CVB vaccine with high immunogenicity capable of preventing CVB-induced diseases.
format Online
Article
Text
id pubmed-7202868
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher American Association for the Advancement of Science
record_format MEDLINE/PubMed
spelling pubmed-72028682020-06-02 A hexavalent Coxsackievirus B vaccine is highly immunogenic and has a strong protective capacity in mice and nonhuman primates Stone, V. M. Hankaniemi, M. M. Laitinen, O. H. Sioofy-Khojine, A. B. Lin, A. Diaz Lozano, I. M. Mazur, M. A. Marjomäki, V. Loré, K. Hyöty, H. Hytönen, V. P. Flodström-Tullberg, M. Sci Adv Research Articles Coxsackievirus B (CVB) enteroviruses are common human pathogens known to cause severe diseases including myocarditis, chronic dilated cardiomyopathy, and aseptic meningitis. CVBs are also hypothesized to be a causal factor in type 1 diabetes. Vaccines against CVBs are not currently available, and here we describe the generation and preclinical testing of a novel hexavalent vaccine targeting the six known CVB serotypes. We show that the vaccine has an excellent safety profile in murine models and nonhuman primates and that it induces strong neutralizing antibody responses to the six serotypes in both species without an adjuvant. We also demonstrate that the vaccine provides immunity against acute CVB infections in mice, including CVB infections known to cause virus-induced myocarditis. In addition, it blocks CVB-induced diabetes in a genetically permissive mouse model. Our preclinical proof-of-concept studies demonstrate the successful generation of a promising hexavalent CVB vaccine with high immunogenicity capable of preventing CVB-induced diseases. American Association for the Advancement of Science 2020-05-06 /pmc/articles/PMC7202868/ /pubmed/32494709 http://dx.doi.org/10.1126/sciadv.aaz2433 Text en Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (http://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Research Articles
Stone, V. M.
Hankaniemi, M. M.
Laitinen, O. H.
Sioofy-Khojine, A. B.
Lin, A.
Diaz Lozano, I. M.
Mazur, M. A.
Marjomäki, V.
Loré, K.
Hyöty, H.
Hytönen, V. P.
Flodström-Tullberg, M.
A hexavalent Coxsackievirus B vaccine is highly immunogenic and has a strong protective capacity in mice and nonhuman primates
title A hexavalent Coxsackievirus B vaccine is highly immunogenic and has a strong protective capacity in mice and nonhuman primates
title_full A hexavalent Coxsackievirus B vaccine is highly immunogenic and has a strong protective capacity in mice and nonhuman primates
title_fullStr A hexavalent Coxsackievirus B vaccine is highly immunogenic and has a strong protective capacity in mice and nonhuman primates
title_full_unstemmed A hexavalent Coxsackievirus B vaccine is highly immunogenic and has a strong protective capacity in mice and nonhuman primates
title_short A hexavalent Coxsackievirus B vaccine is highly immunogenic and has a strong protective capacity in mice and nonhuman primates
title_sort hexavalent coxsackievirus b vaccine is highly immunogenic and has a strong protective capacity in mice and nonhuman primates
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202868/
https://www.ncbi.nlm.nih.gov/pubmed/32494709
http://dx.doi.org/10.1126/sciadv.aaz2433
work_keys_str_mv AT stonevm ahexavalentcoxsackievirusbvaccineishighlyimmunogenicandhasastrongprotectivecapacityinmiceandnonhumanprimates
AT hankaniemimm ahexavalentcoxsackievirusbvaccineishighlyimmunogenicandhasastrongprotectivecapacityinmiceandnonhumanprimates
AT laitinenoh ahexavalentcoxsackievirusbvaccineishighlyimmunogenicandhasastrongprotectivecapacityinmiceandnonhumanprimates
AT sioofykhojineab ahexavalentcoxsackievirusbvaccineishighlyimmunogenicandhasastrongprotectivecapacityinmiceandnonhumanprimates
AT lina ahexavalentcoxsackievirusbvaccineishighlyimmunogenicandhasastrongprotectivecapacityinmiceandnonhumanprimates
AT diazlozanoim ahexavalentcoxsackievirusbvaccineishighlyimmunogenicandhasastrongprotectivecapacityinmiceandnonhumanprimates
AT mazurma ahexavalentcoxsackievirusbvaccineishighlyimmunogenicandhasastrongprotectivecapacityinmiceandnonhumanprimates
AT marjomakiv ahexavalentcoxsackievirusbvaccineishighlyimmunogenicandhasastrongprotectivecapacityinmiceandnonhumanprimates
AT lorek ahexavalentcoxsackievirusbvaccineishighlyimmunogenicandhasastrongprotectivecapacityinmiceandnonhumanprimates
AT hyotyh ahexavalentcoxsackievirusbvaccineishighlyimmunogenicandhasastrongprotectivecapacityinmiceandnonhumanprimates
AT hytonenvp ahexavalentcoxsackievirusbvaccineishighlyimmunogenicandhasastrongprotectivecapacityinmiceandnonhumanprimates
AT flodstromtullbergm ahexavalentcoxsackievirusbvaccineishighlyimmunogenicandhasastrongprotectivecapacityinmiceandnonhumanprimates
AT stonevm hexavalentcoxsackievirusbvaccineishighlyimmunogenicandhasastrongprotectivecapacityinmiceandnonhumanprimates
AT hankaniemimm hexavalentcoxsackievirusbvaccineishighlyimmunogenicandhasastrongprotectivecapacityinmiceandnonhumanprimates
AT laitinenoh hexavalentcoxsackievirusbvaccineishighlyimmunogenicandhasastrongprotectivecapacityinmiceandnonhumanprimates
AT sioofykhojineab hexavalentcoxsackievirusbvaccineishighlyimmunogenicandhasastrongprotectivecapacityinmiceandnonhumanprimates
AT lina hexavalentcoxsackievirusbvaccineishighlyimmunogenicandhasastrongprotectivecapacityinmiceandnonhumanprimates
AT diazlozanoim hexavalentcoxsackievirusbvaccineishighlyimmunogenicandhasastrongprotectivecapacityinmiceandnonhumanprimates
AT mazurma hexavalentcoxsackievirusbvaccineishighlyimmunogenicandhasastrongprotectivecapacityinmiceandnonhumanprimates
AT marjomakiv hexavalentcoxsackievirusbvaccineishighlyimmunogenicandhasastrongprotectivecapacityinmiceandnonhumanprimates
AT lorek hexavalentcoxsackievirusbvaccineishighlyimmunogenicandhasastrongprotectivecapacityinmiceandnonhumanprimates
AT hyotyh hexavalentcoxsackievirusbvaccineishighlyimmunogenicandhasastrongprotectivecapacityinmiceandnonhumanprimates
AT hytonenvp hexavalentcoxsackievirusbvaccineishighlyimmunogenicandhasastrongprotectivecapacityinmiceandnonhumanprimates
AT flodstromtullbergm hexavalentcoxsackievirusbvaccineishighlyimmunogenicandhasastrongprotectivecapacityinmiceandnonhumanprimates