Strength and durability of indirect protection against SARS-CoV-2 infection through vaccine and infection-acquired immunity

Sophia T. Tan, Isabel Rodríguez-Barraquer, Ada T. Kwan, Seth Blumberg, Hailey J. Park, Justine Hutchinson, David Leidner, Joseph A. Lewnard, David Sears and Nathan C. Lo ()
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Sophia T. Tan: Stanford University
Isabel Rodríguez-Barraquer: University of California
Ada T. Kwan: University of California
Seth Blumberg: University of California
Hailey J. Park: Stanford University
Justine Hutchinson: California Correctional Health Care Services
David Leidner: California Department of Corrections and Rehabilitation
Joseph A. Lewnard: University of California
David Sears: University of California
Nathan C. Lo: Stanford University

Nature Communications, 2025, vol. 16, issue 1, 1-10

Abstract: Abstract Early investigation revealed a reduced risk of SARS-CoV-2 infection among social contacts of COVID-19 vaccinated individuals, referred to as indirect protection. However, indirect protection from SARS-CoV-2 infection-acquired immunity and its comparative strength and durability to vaccine-derived indirect protection in the current epidemiologic context of high levels of vaccination, prior infection, and novel variants are not well characterized. Here, we show that both vaccine-derived and infection-acquired immunity independently yield indirect protection to close social contacts with key differences in their strength and waning. Analyzing anonymized SARS-CoV-2 surveillance data from 9,625 residents in California state prisons from December 2021 to December 2022, we find that vaccine-derived indirect protection against Omicron SARS-CoV-2 infection is strongest within three months of COVID-19 vaccination [30% (95% confidence interval: 20–38%)] with subsequent modest protection. Infection-acquired immunity provides 38% (24–50%) indirect protection for 6 months after SARS-CoV-2 infection, with moderate indirect protection persisting for over one year. Variant-targeted vaccines (bivalent formulation including Omicron subvariants BA.4/BA.5) confer strong indirect protection for at least three months [40% (3–63%)]. These results demonstrate that both vaccine-derived and infection-acquired immunity can reduce SARS-CoV-2 transmission which is important for understanding long-term transmission dynamics and can guide public health intervention, especially in high-risk environments such as prisons.

Date: 2025
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DOI: 10.1038/s41467-024-55029-9

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