Type I interferon shapes the quantity and quality of the anti‐Zika virus antibody response

Abstract

Objectives. Zika virus (ZIKV) is a mosquito-borne flavivirus that reemerged in 2015. The association between ZIKV and neurological complications initiated the development of relevant animal models to understand the mechanisms underlying ZIKV-induced pathologies. Transient inhibition of the type I interferon (IFN) pathway through the use of an IFNAR1-blocking antibody, MAR1-5A3, could efficiently permit active virus replication in immunocompetent animals. Type I IFN signalling is involved in the regulation of humoral responses, and thus, it is crucial to investigate the potential effects of type I IFN blockade towards Bcell responses. Methods. In this study, comparative analysis was conducted using serum samples collected from ZIKV-infected wildtype (WT) animals either administered with or without MAR1-5A3. Results. Serological assays revealed a more robust ZIKV-specific IgG response and subtype switching upon inhibition of type I IFN due to the abundance of antigen availability. This observation was corroborated by an increase in germinal centres, plasma cells and germinal centre B cells. Interestingly, although both groups of animals recognised different B-cell linear epitopes in the E and NS1 regions, there was no difference in neutralising capacity. Further characterisation of these epitopes in the E protein revealed a detrimental role of antibodies that were generated in the absence of type I IFN. Conclusion. This study highlights the role of type I IFN in shaping the anti-ZIKV antibody response to generate beneficial antibodies and will help guide development of better vaccine candidates triggering efficient neutralising antibodies and avoiding detrimental ones.

Maternal Immunity and Vaccination Influence Disease Severity in Progeny in a Novel Mast Cell-Deficient Mouse Model of Severe Dengue

“…Interestingly, the presence of IFN-γ in the absence of Type-I IFNs was found to increase mortality and disease severity at 5 weeks of age in MC-deficient mice born to DENV-immune mothers compared to combined Type-I and –II IFN-deficient MC-deficient animals. Inhibition of Type-I IFN during Zika virus infection in adult mice has been reported to induce a robust Zika virus-specific IgG response and subtype switching [ 45 ]. Interestingly, it has been shown that early and transient restriction of the immune response, such as through transient IFN-blockade, can potentially lead to improved long-term antibody responses in the context of viral vaccines, even though the complete loss of Type-I IFNs is detrimental to antibody responses [ 23 ].…”

Robust anti-SARS-CoV2 single domain antibodies cross neutralize multiple viruses

“…Thus, HSV1 sera samples were collected from infected WT animals whereas PPRV sera samples were collected from infected IFNR À/À mice. Signalling via IFNR influences the magnitude and quantity of induced antibody response has been demonstrated previously (Lee et al, 2020;Swanson et al, 2010). We also measured the neutralizing efficiency of anti-HSV1 or anti-PPRV sera samples or those adsorbed with CSP against both the viruses using plaque assays.…”

Subcapsular sinus macrophages maximize germinal center development in non-draining lymph nodes during blood-borne viral infection

“…1). For these experiments, we used wild-type C57BL/6 mice treated with the anti-IFNAR1 monoclonal antibody (mAb) MAR1-5A3 (28)(29)(30). Administration of MAR1-5A3 mAb allows early ZIKV replication in wild-type adult mice while permitting later GC development without perturbed IFN signaling (30).…”

“…For these experiments, we used wild-type C57BL/6 mice treated with the anti-IFNAR1 monoclonal antibody (mAb) MAR1-5A3 (28)(29)(30). Administration of MAR1-5A3 mAb allows early ZIKV replication in wild-type adult mice while permitting later GC development without perturbed IFN signaling (30). We inoculated MAR1-5A3-mAb-treated mice in the left hind FP and determined viral titers in draining (ipsilateral LNs) and non-draining (contralateral) LNs at 24 hours pi (Fig.…”