A systems biology approach to define SARS-CoV-2 correlates of protection
Abstract Correlates of protection (CoPs) for SARS-CoV-2 have yet to be sufficiently defined. This study uses the machine learning platform, SIMON, to accurately predict the immunological parameters that reduced clinical pathology or viral load following SARS-CoV-2 challenge in a cohort of 90 non-hum...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-04-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-025-01103-2 |
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| _version_ | 1850182030563737600 |
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| author | Caolann Brady Tom Tipton Oliver Carnell Stephanie Longet Karen Gooch Yper Hall Javier Salguero Adriana Tomic Miles Carroll |
| author_facet | Caolann Brady Tom Tipton Oliver Carnell Stephanie Longet Karen Gooch Yper Hall Javier Salguero Adriana Tomic Miles Carroll |
| author_sort | Caolann Brady |
| collection | DOAJ |
| description | Abstract Correlates of protection (CoPs) for SARS-CoV-2 have yet to be sufficiently defined. This study uses the machine learning platform, SIMON, to accurately predict the immunological parameters that reduced clinical pathology or viral load following SARS-CoV-2 challenge in a cohort of 90 non-human primates. We found that anti-SARS-CoV-2 spike antibody and neutralising antibody titres were the best predictors of clinical protection and low viral load in the lung. Since antibodies to SARS-CoV-2 spike showed the greatest association with clinical protection and reduced viral load, we next used SIMON to investigate the immunological features that predict high antibody titres. It was found that a pre-immunisation response to seasonal beta-HCoVs and a high frequency of peripheral intermediate and non-classical monocytes predicted low SARS-CoV-2 spike IgG titres. In contrast, an elevated T cell response as measured by IFNγ ELISpot predicted high IgG titres. Additional predictors of clinical protection and low SARS-CoV-2 burden included a high abundance of peripheral T cells. In contrast, increased numbers of intermediate monocytes predicted clinical pathology and high viral burden in the throat. We also conclude that an immunisation strategy that minimises pathology post-challenge did not necessarily mediate viral control. This would be an important finding to take forward into the development of future vaccines aimed at limiting the transmission of SARS-CoV-2. These results contribute to SARS-CoV-2 CoP definition and shed light on the factors influencing the success of SARS-CoV-2 vaccination. |
| format | Article |
| id | doaj-art-2687f4f6a19445e0babf8fe61a9a1a3d |
| institution | OA Journals |
| issn | 2059-0105 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
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| series | npj Vaccines |
| spelling | doaj-art-2687f4f6a19445e0babf8fe61a9a1a3d2025-08-20T02:17:46ZengNature Portfolionpj Vaccines2059-01052025-04-0110111510.1038/s41541-025-01103-2A systems biology approach to define SARS-CoV-2 correlates of protectionCaolann Brady0Tom Tipton1Oliver Carnell2Stephanie Longet3Karen Gooch4Yper Hall5Javier Salguero6Adriana Tomic7Miles Carroll8Centre for Human Genetics, Nuffield Department of Medicine, University of OxfordCentre for Human Genetics, Nuffield Department of Medicine, University of OxfordUK Health Security Agency; Porton DownCentre for Human Genetics, Nuffield Department of Medicine, University of OxfordUK Health Security Agency; Porton DownUK Health Security Agency; Porton DownUK Health Security Agency; Porton DownNational Emerging Infectious Diseases LaboratoriesCentre for Human Genetics, Nuffield Department of Medicine, University of OxfordAbstract Correlates of protection (CoPs) for SARS-CoV-2 have yet to be sufficiently defined. This study uses the machine learning platform, SIMON, to accurately predict the immunological parameters that reduced clinical pathology or viral load following SARS-CoV-2 challenge in a cohort of 90 non-human primates. We found that anti-SARS-CoV-2 spike antibody and neutralising antibody titres were the best predictors of clinical protection and low viral load in the lung. Since antibodies to SARS-CoV-2 spike showed the greatest association with clinical protection and reduced viral load, we next used SIMON to investigate the immunological features that predict high antibody titres. It was found that a pre-immunisation response to seasonal beta-HCoVs and a high frequency of peripheral intermediate and non-classical monocytes predicted low SARS-CoV-2 spike IgG titres. In contrast, an elevated T cell response as measured by IFNγ ELISpot predicted high IgG titres. Additional predictors of clinical protection and low SARS-CoV-2 burden included a high abundance of peripheral T cells. In contrast, increased numbers of intermediate monocytes predicted clinical pathology and high viral burden in the throat. We also conclude that an immunisation strategy that minimises pathology post-challenge did not necessarily mediate viral control. This would be an important finding to take forward into the development of future vaccines aimed at limiting the transmission of SARS-CoV-2. These results contribute to SARS-CoV-2 CoP definition and shed light on the factors influencing the success of SARS-CoV-2 vaccination.https://doi.org/10.1038/s41541-025-01103-2 |
| spellingShingle | Caolann Brady Tom Tipton Oliver Carnell Stephanie Longet Karen Gooch Yper Hall Javier Salguero Adriana Tomic Miles Carroll A systems biology approach to define SARS-CoV-2 correlates of protection npj Vaccines |
| title | A systems biology approach to define SARS-CoV-2 correlates of protection |
| title_full | A systems biology approach to define SARS-CoV-2 correlates of protection |
| title_fullStr | A systems biology approach to define SARS-CoV-2 correlates of protection |
| title_full_unstemmed | A systems biology approach to define SARS-CoV-2 correlates of protection |
| title_short | A systems biology approach to define SARS-CoV-2 correlates of protection |
| title_sort | systems biology approach to define sars cov 2 correlates of protection |
| url | https://doi.org/10.1038/s41541-025-01103-2 |
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