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

Blake Schouest,Brandon J Beddingfield,Margaret H Gilbert,Rudolf P Bohm,Faith Schiro,Pyone P Aye,Antonito T Panganiban,Diogo M Magnani,Nicholas J Maness

doi:10.1016/j.virol.2021.03.019

Blake Schouest, Brandon J Beddingfield + Show 7 more

Open Access

https://doi.org/10.1016/j.virol.2021.03.019

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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.

Highlights

ZIKV was first isolated nearly seventy years prior to the Brazilian outbreak of 2015 (Dick et al, 1952; Zanluca et al, 2015), but the recent epidemic became associated with vertical transmission dynamics and congenital syndromes that were unprecedented for ZIKV or any other flavivirus (Plourde and Bloch, 2016)
Experimental ZIKV vaccine efforts to date have been successful, with a number of candidate vaccines having advanced to clinical trials, but an often underappreciated consideration in vaccine design is whether protective responses can be attained in the context of pregnancy
The primary infection appeared to confer complete protection in that all animals resisted rechallenge, we carried out transcriptome analysis to assess the quality of immune responses mounted during pregnancy

Summary

Introduction

ZIKV was first isolated nearly seventy years prior to the Brazilian outbreak of 2015 (Dick et al, 1952; Zanluca et al, 2015), but the recent epidemic became associated with vertical transmission dynamics and congenital syndromes that were unprecedented for ZIKV or any other flavivirus (Plourde and Bloch, 2016). Guillain-Barre syndrome, meningitis, and meningoencephalitis, became linked to infection in adults (Araujo et al, 2016; Avelino-Silva and Martin, 2016; Brasil et al, 2016; Ellul et al, 2016), the most severe neurological consequences were documented in infants born to mothers infected during pregnancy (Barton and Salvadori, 2016; Melo et al, 2016). Complex interactions between sex hormones and the immune system make pregnant women more susceptible to a host of infections (Kourtis et al, 2014), so an important question in ZIKV vaccine design is whether immunity induced during pregnancy is sufficient to prevent subsequent infections and if this protection extends to infants born to women infected during pregnancy Several murine and NHP models have been developed to understand mechanisms of maternal-to-fetal transmission and to develop and test antiviral therapies and vaccines (Aliota et al, 2016; Dudley et al, 2016; Hirsch et al, 2017; Koide et al, 2016; Magnani et al, 2018; Morrison and Diamond, 2017; Nguyen et al, 2017; O'Connor et al, 2018; Osuna et al, 2016), but NHPs may provide a superior model to study vertical transmission and congenital hazards due to the similarities in placental structure and gestational development to humans (Morrison and Diamond, 2017).

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