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

Lee, Cheryl Yi-Pin, Carissimo, Guillaume, Chen, Zheyuan, Lum, Fok-Moon, Abu Bakar, Farhana, Rajarethinam, Ravisankar, Teo, Teck-Hui, Torres-Ruesta, Anthony, Renia, Laurent and Ng, Lisa FP ORCID: 0000-0003-4071-5222
(2020) Type I interferon shapes the quantity and quality of the anti-Zika virus antibody response. CLINICAL & TRANSLATIONAL IMMUNOLOGY, 9 (4). e1126-.

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<h4>Objectives</h4>Zika virus (ZIKV) is a mosquito-borne <i>flavivirus</i> that re-emerged 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 B-cell responses.<h4>Methods</h4>In this study, comparative analysis was conducted using serum samples collected from ZIKV-infected wild-type (WT) animals either administered with or without MAR1-5A3.<h4>Results</h4>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.<h4>Conclusion</h4>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.

Item Type: Article
Uncontrolled Keywords: antibodies, humoral response, mouse models, type I interferon, Zika virus
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User: Symplectic Admin
Date Deposited: 17 Jun 2021 09:20
Last Modified: 18 Jan 2023 22:34
DOI: 10.1002/cti2.1126
Open Access URL: https://doi.org/10.1002/cti2.1126
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3126702