Please use this identifier to cite or link to this item:
Type
ArticleCopyright
Open access
Sustainable Development Goals
03 Saúde e Bem-EstarCollections
- IOC - Artigos de Periódicos [12967]
Metadata
Show full item record
YELLOW FEVER VACCINE PROTECTS MICE AGAINST ZIKA VIRUS INFECTION
Author
Affilliation
Abstract
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-
Barre´ 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.
Share