Cargando…
Type I interferon shapes the quantity and quality of the anti‐Zika virus antibody response
OBJECTIVES: Zika virus (ZIKV) is a mosquito‐borne flavivirus 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 i...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184064/ https://www.ncbi.nlm.nih.gov/pubmed/32346479 http://dx.doi.org/10.1002/cti2.1126 |
_version_ | 1783526542285996032 |
---|---|
author | Lee, Cheryl Yi‐Pin Carissimo, Guillaume Chen, Zheyuan Lum, Fok‐Moon Abu Bakar, Farhana Rajarethinam, Ravisankar Teo, Teck‐Hui Torres‐Ruesta, Anthony Renia, Laurent Ng, Lisa FP |
author_facet | Lee, Cheryl Yi‐Pin Carissimo, Guillaume Chen, Zheyuan Lum, Fok‐Moon Abu Bakar, Farhana Rajarethinam, Ravisankar Teo, Teck‐Hui Torres‐Ruesta, Anthony Renia, Laurent Ng, Lisa FP |
author_sort | Lee, Cheryl Yi‐Pin |
collection | PubMed |
description | OBJECTIVES: Zika virus (ZIKV) is a mosquito‐borne flavivirus 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. METHODS: 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. 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. |
format | Online Article Text |
id | pubmed-7184064 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-71840642020-04-28 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 Ng, Lisa FP Clin Transl Immunology Original Article OBJECTIVES: Zika virus (ZIKV) is a mosquito‐borne flavivirus 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. METHODS: 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. 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. John Wiley and Sons Inc. 2020-04-26 /pmc/articles/PMC7184064/ /pubmed/32346479 http://dx.doi.org/10.1002/cti2.1126 Text en © 2020 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Lee, Cheryl Yi‐Pin Carissimo, Guillaume Chen, Zheyuan Lum, Fok‐Moon Abu Bakar, Farhana Rajarethinam, Ravisankar Teo, Teck‐Hui Torres‐Ruesta, Anthony Renia, Laurent Ng, Lisa FP Type I interferon shapes the quantity and quality of the anti‐Zika virus antibody response |
title | Type I interferon shapes the quantity and quality of the anti‐Zika virus antibody response |
title_full | Type I interferon shapes the quantity and quality of the anti‐Zika virus antibody response |
title_fullStr | Type I interferon shapes the quantity and quality of the anti‐Zika virus antibody response |
title_full_unstemmed | Type I interferon shapes the quantity and quality of the anti‐Zika virus antibody response |
title_short | Type I interferon shapes the quantity and quality of the anti‐Zika virus antibody response |
title_sort | type i interferon shapes the quantity and quality of the anti‐zika virus antibody response |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184064/ https://www.ncbi.nlm.nih.gov/pubmed/32346479 http://dx.doi.org/10.1002/cti2.1126 |
work_keys_str_mv | AT leecherylyipin typeiinterferonshapesthequantityandqualityoftheantizikavirusantibodyresponse AT carissimoguillaume typeiinterferonshapesthequantityandqualityoftheantizikavirusantibodyresponse AT chenzheyuan typeiinterferonshapesthequantityandqualityoftheantizikavirusantibodyresponse AT lumfokmoon typeiinterferonshapesthequantityandqualityoftheantizikavirusantibodyresponse AT abubakarfarhana typeiinterferonshapesthequantityandqualityoftheantizikavirusantibodyresponse AT rajarethinamravisankar typeiinterferonshapesthequantityandqualityoftheantizikavirusantibodyresponse AT teoteckhui typeiinterferonshapesthequantityandqualityoftheantizikavirusantibodyresponse AT torresruestaanthony typeiinterferonshapesthequantityandqualityoftheantizikavirusantibodyresponse AT renialaurent typeiinterferonshapesthequantityandqualityoftheantizikavirusantibodyresponse AT nglisafp typeiinterferonshapesthequantityandqualityoftheantizikavirusantibodyresponse |