Yellow fever vaccine protects mice against Zika virus infection.

Zika virus (ZIKV) emerged as an important infectious disease agent in Brazil in 2016. Infection usually leads to mild symptoms, but severe congenital neurological disorders and Guillain-Barré syndrome have been reported following ZIKV exposure. Creating an effective vaccine against ZIKV is a public...

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Autores principales:	Ana C Vicente Santos, Francisca H Guedes-da-Silva, Carlos H Dumard, Vivian N S Ferreira, Igor P S da Costa, Ruana A Machado, Fernanda G Q Barros-Aragão, Rômulo L S Neris, Júlio S Dos-Santos, Iranaia Assunção-Miranda, Claudia P Figueiredo, André A Dias, Andre M O Gomes, Herbert L de Matos Guedes, Andrea C Oliveira, Jerson L Silva
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/9a0c189268f04faf98a26350189d234f
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spelling	oai:doaj.org-article:9a0c189268f04faf98a26350189d234f2021-12-02T20:23:59ZYellow fever vaccine protects mice against Zika virus infection.1935-27271935-273510.1371/journal.pntd.0009907https://doaj.org/article/9a0c189268f04faf98a26350189d234f2021-11-01T00:00:00Zhttps://doi.org/10.1371/journal.pntd.0009907https://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735Zika virus (ZIKV) emerged as an important infectious disease agent in Brazil in 2016. Infection usually leads to mild symptoms, but severe congenital neurological disorders and Guillain-Barré syndrome have been reported following ZIKV exposure. Creating an effective vaccine against ZIKV is a public health priority. We describe the protective effect of an already licensed attenuated yellow fever vaccine (YFV, 17DD) in type-I interferon receptor knockout mice (A129) and immunocompetent BALB/c and SV-129 (A129 background) mice infected with ZIKV. YFV vaccination provided protection against ZIKV, with decreased mortality in A129 mice, a reduction in the cerebral viral load in all mice, and weight loss prevention in BALB/c mice. The A129 mice that were challenged two and three weeks after the first dose of the vaccine were fully protected, whereas partial protection was observed five weeks after vaccination. In all cases, the YFV vaccine provoked a substantial decrease in the cerebral viral load. YFV immunization also prevented hippocampal synapse loss and microgliosis in ZIKV-infected mice. Our vaccine model is T cell-dependent, with AG129 mice being unable to tolerate immunization (vaccination is lethal in this mouse model), indicating the importance of IFN-γ in immunogenicity. To confirm the role of T cells, we immunized nude mice that we demonstrated to be very susceptible to infection. Immunization with YFV and challenge 7 days after booster did not protect nude mice in terms of weight loss and showed partial protection in the survival curve. When we evaluated the humoral response, the vaccine elicited significant antibody titers against ZIKV; however, it showed no neutralizing activity in vitro and in vivo. The data indicate that a cell-mediated response promotes protection against cerebral infection, which is crucial to vaccine protection, and it appears to not necessarily require a humoral response. This protective effect can also be attributed to innate factors, but more studies are needed to strengthen this hypothesis. Our findings open the way to using an available and inexpensive vaccine for large-scale immunization in the event of a ZIKV outbreak.Ana C Vicente SantosFrancisca H Guedes-da-SilvaCarlos H DumardVivian N S FerreiraIgor P S da CostaRuana A MachadoFernanda G Q Barros-AragãoRômulo L S NerisJúlio S Dos-SantosIranaia Assunção-MirandaClaudia P FigueiredoAndré A DiasAndre M O GomesHerbert L de Matos GuedesAndrea C OliveiraJerson L SilvaPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 15, Iss 11, p e0009907 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
spellingShingle	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Ana C Vicente Santos Francisca H Guedes-da-Silva Carlos H Dumard Vivian N S Ferreira Igor P S da Costa Ruana A Machado Fernanda G Q Barros-Aragão Rômulo L S Neris Júlio S Dos-Santos Iranaia Assunção-Miranda Claudia P Figueiredo André A Dias Andre M O Gomes Herbert L de Matos Guedes Andrea C Oliveira Jerson L Silva Yellow fever vaccine protects mice against Zika virus infection.
description	Zika virus (ZIKV) emerged as an important infectious disease agent in Brazil in 2016. Infection usually leads to mild symptoms, but severe congenital neurological disorders and Guillain-Barré syndrome have been reported following ZIKV exposure. Creating an effective vaccine against ZIKV is a public health priority. We describe the protective effect of an already licensed attenuated yellow fever vaccine (YFV, 17DD) in type-I interferon receptor knockout mice (A129) and immunocompetent BALB/c and SV-129 (A129 background) mice infected with ZIKV. YFV vaccination provided protection against ZIKV, with decreased mortality in A129 mice, a reduction in the cerebral viral load in all mice, and weight loss prevention in BALB/c mice. The A129 mice that were challenged two and three weeks after the first dose of the vaccine were fully protected, whereas partial protection was observed five weeks after vaccination. In all cases, the YFV vaccine provoked a substantial decrease in the cerebral viral load. YFV immunization also prevented hippocampal synapse loss and microgliosis in ZIKV-infected mice. Our vaccine model is T cell-dependent, with AG129 mice being unable to tolerate immunization (vaccination is lethal in this mouse model), indicating the importance of IFN-γ in immunogenicity. To confirm the role of T cells, we immunized nude mice that we demonstrated to be very susceptible to infection. Immunization with YFV and challenge 7 days after booster did not protect nude mice in terms of weight loss and showed partial protection in the survival curve. When we evaluated the humoral response, the vaccine elicited significant antibody titers against ZIKV; however, it showed no neutralizing activity in vitro and in vivo. The data indicate that a cell-mediated response promotes protection against cerebral infection, which is crucial to vaccine protection, and it appears to not necessarily require a humoral response. This protective effect can also be attributed to innate factors, but more studies are needed to strengthen this hypothesis. Our findings open the way to using an available and inexpensive vaccine for large-scale immunization in the event of a ZIKV outbreak.
format	article
author	Ana C Vicente Santos Francisca H Guedes-da-Silva Carlos H Dumard Vivian N S Ferreira Igor P S da Costa Ruana A Machado Fernanda G Q Barros-Aragão Rômulo L S Neris Júlio S Dos-Santos Iranaia Assunção-Miranda Claudia P Figueiredo André A Dias Andre M O Gomes Herbert L de Matos Guedes Andrea C Oliveira Jerson L Silva
author_facet	Ana C Vicente Santos Francisca H Guedes-da-Silva Carlos H Dumard Vivian N S Ferreira Igor P S da Costa Ruana A Machado Fernanda G Q Barros-Aragão Rômulo L S Neris Júlio S Dos-Santos Iranaia Assunção-Miranda Claudia P Figueiredo André A Dias Andre M O Gomes Herbert L de Matos Guedes Andrea C Oliveira Jerson L Silva
author_sort	Ana C Vicente Santos
title	Yellow fever vaccine protects mice against Zika virus infection.
title_short	Yellow fever vaccine protects mice against Zika virus infection.
title_full	Yellow fever vaccine protects mice against Zika virus infection.
title_fullStr	Yellow fever vaccine protects mice against Zika virus infection.
title_full_unstemmed	Yellow fever vaccine protects mice against Zika virus infection.
title_sort	yellow fever vaccine protects mice against zika virus infection.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/9a0c189268f04faf98a26350189d234f
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Yellow fever vaccine protects mice against Zika virus infection.

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