Comparative IgG responses to SARS-CoV-2 after natural infection or vaccination

Abstract

Background: Whether vaccination or natural infection provides greater benefit regarding the development of sustained immunity against SARS-CoV-2 remains unknown. Therefore, the aim of this study was to provide a direct comparison of IgG durability and neutralizing antibody (NAb) levels in vaccinated and unvaccinated adults. Methods: This was a prospective, cross-sectional study of antibody durability in 1087 individuals with a median (IQR) age of 42 (35, 52) years who were unvaccinated and previously infected with SARS-CoV-2 (Arm 1, n=351) or vaccinated against the virus (Arm 2, n=737). Participants self-reported vaccination and infection history and provided self-collected serology samples using mailed collection kits. Results: Anti-S1 IgG seroprevalence was 15.6% higher in vaccinated versus unvaccinated, previously-infected individuals across intervals ranging from 1 to 12 months and antibody survival was sustained near 100% through 12 months in the vaccinated group. NAb titers at 50% inhibition were significantly greater in vaccinated individuals with values that averaged 893.0 units higher than those observed in the unvaccinated, naturally infected group. Conclusions: These findings suggest that vaccination as opposed to natural infection alone provides significant advantages in terms of sustained and effective (neutralizing) immunity against prior variants of SARS-CoV-2. Future efforts to characterize SARS-CoV-2 immune responses should address hybrid immunity, booster status and formulation, and protection against (sub)variants of Omicron and future lineages, as well as weigh the potential impact of other immune system mechanisms.