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 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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Clinical & Translational Immunology |
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| Online Access: | https://doi.org/10.1002/cti2.1126 |
| _version_ | 1819091930896662528 |
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| author | Cheryl Yi‐Pin Lee Guillaume Carissimo Zheyuan Chen Fok‐Moon Lum Farhana Abu Bakar Ravisankar Rajarethinam Teck‐Hui Teo Anthony Torres‐Ruesta Laurent Renia Lisa FP Ng |
| author_facet | Cheryl Yi‐Pin Lee Guillaume Carissimo Zheyuan Chen Fok‐Moon Lum Farhana Abu Bakar Ravisankar Rajarethinam Teck‐Hui Teo Anthony Torres‐Ruesta Laurent Renia Lisa FP Ng |
| author_sort | Cheryl Yi‐Pin Lee |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-21T22:47:33Z |
| format | Article |
| id | doaj.art-b8a839d561b54504bf803e14695dd033 |
| institution | Directory Open Access Journal |
| issn | 2050-0068 |
| language | English |
| last_indexed | 2024-12-21T22:47:33Z |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical & Translational Immunology |
| spelling | doaj.art-b8a839d561b54504bf803e14695dd0332022-12-21T18:47:40ZengWileyClinical & Translational Immunology2050-00682020-01-0194n/an/a10.1002/cti2.1126Type I interferon shapes the quantity and quality of the anti‐Zika virus antibody responseCheryl Yi‐Pin Lee0Guillaume Carissimo1Zheyuan Chen2Fok‐Moon Lum3Farhana Abu Bakar4Ravisankar Rajarethinam5Teck‐Hui Teo6Anthony Torres‐Ruesta7Laurent Renia8Lisa FP Ng9Singapore Immunology Network Agency for Science, Technology and Research (A*STAR) SingaporeSingapore Immunology Network Agency for Science, Technology and Research (A*STAR) SingaporeSingapore Immunology Network Agency for Science, Technology and Research (A*STAR) SingaporeSingapore Immunology Network Agency for Science, Technology and Research (A*STAR) SingaporeSingapore Immunology Network Agency for Science, Technology and Research (A*STAR) SingaporeInstitute of Molecular and Cell Biology Agency of Science, Technology and Research (A*STAR) SingaporeSingapore Immunology Network Agency for Science, Technology and Research (A*STAR) SingaporeSingapore Immunology Network Agency for Science, Technology and Research (A*STAR) SingaporeSingapore Immunology Network Agency for Science, Technology and Research (A*STAR) SingaporeSingapore Immunology Network Agency for Science, Technology and Research (A*STAR) SingaporeAbstract 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.https://doi.org/10.1002/cti2.1126antibodieshumoral responsemouse modelstype I interferonZika virus |
| spellingShingle | Cheryl Yi‐Pin Lee Guillaume Carissimo Zheyuan Chen Fok‐Moon Lum Farhana Abu Bakar Ravisankar Rajarethinam Teck‐Hui Teo Anthony Torres‐Ruesta Laurent Renia Lisa FP Ng Type I interferon shapes the quantity and quality of the anti‐Zika virus antibody response Clinical & Translational Immunology antibodies humoral response mouse models type I interferon Zika virus |
| 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 | antibodies humoral response mouse models type I interferon Zika virus |
| url | https://doi.org/10.1002/cti2.1126 |
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