Informing risk stratification and vaccine policy via a predictive mathematical model of SARS-COV-2 infection

Abstract

SARS-CoV-2 human challenge studies enabled unprecedented high frequency temporal measurements of immune determinants of viral control. We integrated prior knowledge of SARS-CoV-2 replication, innate, cytotoxic T cell and antibody responses into a dynamic model which captured viral-load kinetics in seronegative volunteers challenged with wildtype virus. The model predicted measured innate and adaptive immune dynamics. Perturbation analyses indicated that innate immunity limits peak viral load, whereas antibodies principally mediate clearance while cytotoxic T cells become critical in antibody deficiency. Pre-existing antibodies suppressed both viral replication and subsequent immune activation- a prediction validated in a second challenge study of seropositive participants infected with the SARS-CoV-2 Delta variant. The model explains how specific immunodeficiencies may increase susceptibility to severe or persistent infection, supporting clinical risk stratification. It suggests that T cell-targeted vaccination strategies may provide limited protection without effective neutralising antibodies, and that attenuated boosting after low-dose exposure requires repeated vaccination to reduce breakthrough infections, informing public health policy.

One Sentence SummaryA mathematical model of SARS-COV-2 infection predicts innate and adaptive immunity, and informs risk stratification and vaccine policy.

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BibTeX RIS

BibTeX

@misc{chain2026informing,
  title = {{Informing risk stratification and vaccine policy via a predictive mathematical model of SARS-COV-2 infection}},
  author = {B. Chain and C. Callan and D. Scobie and M. Cowley and J. Jang and R. Gupta and C. Turner and J. Rosenheim and C. Thakker and L. Bell and G. Nageswaran and S. Byrne and B. Killingley and A. Boyers and M. Kalinova and a. Catchpole and A. Mann and R. Lindeboom and M. Nikolic and S. Teichmann and H. Wagstaffe and A. Tiffeau-Mayer and C. Chiu and M. Nousadeghi},
  howpublished = {medRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.12.26365315},
  url = {https://www.medrxiv.org/content/10.64898/2026.10.12.26365315v1},
  note = {CC BY-NC},
}

RIS

TY  - UNPB
TI  - Informing risk stratification and vaccine policy via a predictive mathematical model of SARS-COV-2 infection
AU  - B. Chain
AU  - C. Callan
AU  - D. Scobie
AU  - M. Cowley
AU  - J. Jang
AU  - R. Gupta
AU  - C. Turner
AU  - J. Rosenheim
AU  - C. Thakker
AU  - L. Bell
AU  - G. Nageswaran
AU  - S. Byrne
AU  - B. Killingley
AU  - A. Boyers
AU  - M. Kalinova
AU  - a. Catchpole
AU  - A. Mann
AU  - R. Lindeboom
AU  - M. Nikolic
AU  - S. Teichmann
AU  - H. Wagstaffe
AU  - A. Tiffeau-Mayer
AU  - C. Chiu
AU  - M. Nousadeghi
PY  - 2026
DA  - 2026/10/12
PB  - medRxiv
DO  - 10.64898/2026.10.12.26365315
UR  - https://www.medrxiv.org/content/10.64898/2026.10.12.26365315v1
AB  - SARS-CoV-2 human challenge studies enabled unprecedented high frequency temporal measurements of immune determinants of viral control. We integrated prior knowledge of SARS-CoV-2 replication, innate, cytotoxic T cell and antibody responses into a dynamic model which captured viral-load kinetics in seronegative volunteers challenged with wildtype virus. The model predicted measured innate and adaptive immune dynamics. Perturbation analyses indicated that innate immunity limits peak viral load, whereas antibodies principally mediate clearance while cytotoxic T cells become critical in antibody deficiency. Pre-existing antibodies suppressed both viral replication and subsequent immune activation- a prediction validated in a second challenge study of seropositive participants infected with the SARS-CoV-2 Delta variant. The model explains how specific immunodeficiencies may increase susceptibility to severe or persistent infection, supporting clinical risk stratification. It suggests that T cell-targeted vaccination strategies may provide limited protection without effective neutralising antibodies, and that attenuated boosting after low-dose exposure requires repeated vaccination to reduce breakthrough infections, informing public health policy.  One Sentence SummaryA mathematical model of SARS-COV-2 infection predicts innate and adaptive immunity, and informs risk stratification and vaccine policy.
ER  -

Abstract

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