An Epidemic Zika Virus Isolate Drives Enhanced T Follicular Helper Cell and B Cell–Mediated Immunity

Abstract

Zika virus (ZIKV) is a mosquito-borne pathogen that recently caused a series of increasingly severe outbreaks. We previously demonstrated that, compared with a pre-epidemic isolate (ZIKVCDN), a Brazilian ZIKV isolate (ZIKVBR) possesses a novel capacity to suppress host immunity, resulting in delayed viral clearance. However, whether ZIKVBR modulates CD4 T cell responses remains unknown. In this study, we show that, in comparison with ZIKVCDN infection, CD4 T cells are less polarized to the Th1 subtype following ZIKVBR challenge in mice. In contrast, we observed an enhanced accumulation of T follicular helper cells 10, 14, and 21 d postinfection with ZIKVBR. This response correlated with an enhanced germinal center B cell response and robust production of higher avidity-neutralizing Abs following ZIKVBR infection. Taken together, our data suggest that contemporary ZIKV strains have evolved to differentially induce CD4 T cell, B cell, and Ab responses and this could provide a model to further define the signals required for T follicular helper cell development.

Ipsilateral immunization after a prior SARS-CoV-2 mRNA vaccination elicits superior B cell responses compared to contralateral immunization

“…The affinity-ELISA assay was conducted as described in a previous study. 41 Briefly, based on the above protocol, various concentrations of ammonium thiocyanate (0.15–4 M range) were added into the wells and incubated for 15 min prior to adding the IgG incubation. The plates were developed with TMB substrate solution (Thermo Scientific, Cat: 34021) and quenched with 2N sulfuric acid prior to measurement at 450nm with a microplate reader (BioTek).…”

CD4+ T Cell Depletion Before Primary Dengue and/or Secondary Zika Infection Reveals Mechanistic Correlates of Antibody Functionality in Rhesus Macaques

“…Pardy et al showed that CD4 + T cells were differentially polarized to the Th1 subtype after challenging mice with pre-epidemic or contemporary ZIKV strains. The differences were characterized by enhanced GC B cell response and robust production of higher avidity-nAbs following the infection with the contemporary strain, suggesting that ZIKV strains have evolved to differentially induce T cell, B cell, and Ab responses including their avidity and neutralization properties (Pardy et al, 2022). These results are relevant while considering ZIKV vaccine designs.…”

“…These cells have been described, in terms of function, as the equivalent counterpart of germinal center (GC) Tfh cells in peripheral blood (Bentebibel et al, 2013; Crotty, 2014; Morita et al, 2011). However, there is limited literature available on the role of pTfh cells in DENV (Haltaufderhyde et al, 2018; Izmirly et al, 2022; Wijesinghe et al, 2020) and ZIKV vaccination or infections (Liang et al, 2019; Pardy et al, 2022). Despite their critical role helping B cells form an optimal humoral immune response, there are scarce works studying the direct interactions of CD4 + T cells/pTfh cells subsets with B cells and NS proteins, and its effect in Abs functionality against DENV and/or ZIKV (Elong Ngono et al, 2019; Rivino et al, 2013; Rouers et al, 2021).…”