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-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.
Highlights
Zika virus (ZIKV) probably emerged in the early 1900s and remained undetected for several years [1]
Our study reports that the current attenuated yellow fever vaccine is effective in immunizing against the infection caused by the Zika virus, due to the similarity between the two viruses
We demonstrate that the yellow fever virus (YFV) vaccine elicits an immune response that protects against cerebral infection by ZIKV
Summary
Zika virus (ZIKV) probably emerged in the early 1900s and remained undetected for several years [1]. This virus was first isolated in 1947 from a sentinel rhesus monkey (Macaca mulatta) presenting with a febrile illness in the Zika Forest of Uganda [2]. The first case of ZIKV in humans was reported in 1952 [3], and ZIKV was historically regarded as a self-limiting disease. The scenario began to change in 2013, when a large outbreak in French Polynesia was associated with cases of Guillain-Barresyndrome [4]; during an outbreak in Brazil (2014– 2015), authorities reported an increased number of children born with microcephaly [1,5]. ZIKV infection is known to be associated with congenital malformations and other neurological complications, such as Guillain-Barresyndrome [6,7]. The epidemiological scenario of ZIKV has expanded quickly and has been considered endemic in Latin America and in Caribbean regions and in parts of Africa and Asia [8]
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