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

Early investigation revealed that COVID-19 vaccines confer indirect protection to fully susceptible and unvaccinated persons, defined as a reduced risk of SARS-CoV-2 infection among social contacts of vaccinated individuals. However, indirect protection from 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 infection-acquired and vaccine-derived immunity independently yield indirect protection to close social contacts with key differences in their strength and waning. Analyzing anonymized data from a system-wide SARS-CoV-2 surveillance program of 177,319 residents across 35 California state prisons from December 2021 to December 2022 in a case-control design, we find that vaccine-derived indirect protection against Omicron SARS-CoV-2 infection is strongest within three months post-vaccination [30% (95% confidence interval: 20-38%)] with subsequent modest protection, whereas infection-acquired immunity provides 38% (24-50%) indirect protection to roommates 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 have important implications for understanding the long-term transmission dynamics of SARS-CoV-2 and can guide vaccine policy and public health measures, especially in high-risk environments such as prisons.