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Zika virus infection during pregnancy protects against secondary infection in the absence of CD8⁺ cells.

ABSTRACT: While T cell immunity is an important component of the immune response to Zika virus (ZIKV) infection generally, the efficacy of these responses during pregnancy remains unknown. Here, we tested the capacity of CD8 lymphocytes to protect from secondary challenge in four macaques, two of which were depleted of CD8⁺ cells prior to rechallenge with a heterologous ZIKV isolate. The initial challenge during pregnancy produced transcriptional signatures suggesting complex patterns of immune modulation as well as neutralizing antibodies that persisted until rechallenge, which all animals efficiently controlled, demonstrating that the primary infection conferred adequate protection. The secondary challenge promoted activation of innate and adaptive immune cells, possibly suggesting a brief period of infection prior to clearance. These data confirm that ZIKV infection during pregnancy induces sufficient immunity to protect from a secondary challenge and suggest that this protection is not dependent on CD8 T cells.

SUBMITTER: Schouest B

PROVIDER: S-EPMC8212702 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Zika virus infection during pregnancy protects against secondary infection in the absence of CD8<sup>+</sup> cells.

Schouest Blake B Beddingfield Brandon J BJ Gilbert Margaret H MH Bohm Rudolf P RP Schiro Faith F Aye Pyone P PP Panganiban Antonito T AT Magnani Diogo M DM Maness Nicholas J NJ

Virology 20210409

While T cell immunity is an important component of the immune response to Zika virus (ZIKV) infection generally, the efficacy of these responses during pregnancy remains unknown. Here, we tested the capacity of CD8 lymphocytes to protect from secondary challenge in four macaques, two of which were depleted of CD8<sup>+</sup> cells prior to rechallenge with a heterologous ZIKV isolate. The initial challenge during pregnancy produced transcriptional signatures suggesting complex patterns of immune ...[more]

PMID: 33865073

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Project 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.

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Zika virus infection during pregnancy protects against secondary infection in the absence of CD8⁺ cells.

Publications

Zika virus infection during pregnancy protects against secondary infection in the absence of CD8<sup>+</sup> cells.

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Zika virus infection during pregnancy protects against secondary infection in the absence of CD8+ cells.

Publications

Zika virus infection during pregnancy protects against secondary infection in the absence of CD8<sup>+</sup> cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Zika virus infection during pregnancy protects against secondary infection in the absence of CD8⁺ cells.