Abstract
BACKGROUND: Data suggest that antibody responses following COVID-19 vaccines are a correlate of protection. Some studies, including the clinical trials of COVID-19 mRNA vaccines, did not stratify and evaluate whether antibody responses to COVID-19 vaccines differed between the sexes or with aging. This gap in research is particularly relevant for older populations such as nursing home residents (NHR). We hypothesized that sex differences in vaccine-induced antibody responses may intersect with age and be diminished among older adults residing in nursing homes. METHODS: We analyzed serum samples from 638 NHRs collected serially after the primary two-dose series and three subsequent booster doses of mRNA SARS-CoV-2 vaccinations. We analyzed anti-Spike IgG and neutralizing antibody titers to the Wuhan and Omicron BA.4/5 variant strains. Mixed-effects models predicting log-transformed titers were estimated to compare responses across vaccine doses, focusing on sex-differential responses. For detected post-dose sex differences, additional sample times were analyzed to assess the duration of the difference. RESULTS: Following the primary series, female NHRs with a prior history of SARS-CoV-2 infection had significantly higher Wuhan anti-Spike antibodies and neutralizing antibody titers than male NHRs with differences persisting up to nine months post-vaccination. Subsequent monovalent booster doses and a bivalent booster dose eliminated this disparity. We did not detect any differential response to the Omicron BA.4/5 variant. CONCLUSIONS: The blunting of sex differences in antibody response observed following the primary series by the 1st booster dose underscores the importance of booster vaccination in this population.