A systems biology approach to define SARS-CoV-2 correlates of protection

被引：0

作者：

Brady, Caolann ^{[1
,2
]}

Tipton, Tom ^{[1
,2
]}

Carnell, Oliver ^{[3
]}

Longet, Stephanie ^{[1
,2
,4
]}

Gooch, Karen ^{[3
]}

Hall, Yper ^{[3
]}

Salguero, Javier ^{[3
]}

Tomic, Adriana ^{[5
,6
,7
]}

Carroll, Miles ^{[1
,2
]}

机构：

[1] Univ Oxford, Ctr Human Genet, Nuffield Dept Med, Oxford, England

[2] Univ Oxford, Pandem Sci Inst, Oxford, England

[3] UK Hlth Secur Agcy, Porton Down, Salisbury, England

[4] Claude Bernard Lyon 1 Univ, Int Ctr Infectiol Res CIRI, Team GIMAP, St Etienne, France

[5] Natl Emerging Infect Dis Labs, Boston, MA USA

[6] Boston Univ, Dept Virol Immunol & Microbiol, Med Sch, Boston, MA USA

[7] Boston Univ, Coll Engn, Biomed Engn, Boston, MA USA

来源：

NPJ VACCINES | 2025年 / 10卷 / 01期

关键词：

BORDETELLA-PERTUSSIS; INFECTION; ANTIBODIES; IMMUNITY; VACCINE; CELLS;

D O I：

10.1038/s41541-025-01103-2

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 IFN gamma 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.

引用

页数：15

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