Older adults were disproportionately affected during the COVID-19 pandemic, and while many vaccine clinical trials included older adults, they failed to include those who were particularly old or frail. Immunosenescence, or the process of declining immune function with age, greatly affects susceptibility to infections. Evidence suggests that the effects of aging on the immune system differs between the sexes. Understanding immunosenescence is crucial for vaccine development and implementation in older populations to induce a robust immune response for protection against infectious disease. This study characterized the intersection of sex and aging on the antibody response to the Moderna and Pfizer COVID-19 vaccines.
To characterize the immune response in older adults, plasma samples were collected from vaccinees aged 75-98 years old before and after 3 doses and from younger adults aged 18-74 years old before and after 2 doses. Key antibody characteristics, such as antibody binding to antigens and virus neutralization, were measured against the vaccine virus and variants of concern (Alpha, Delta, and Omicron). Additionally, the established Fried frailty phenotype was used to assess participant’s frailty status.
Results of this research identified key differences in the immune response between females and males across the lifespan, as well as the impact of advanced age on vaccine-induced immunity. In both cohorts, vaccination induced a more robust antibody response in females compared to males. Furthermore, the younger cohort had higher measured antibody responses relative to the older cohort. Age and frailty were both associated with lower antibody response in males but interestingly, not in females. Older females also maintained higher antibody response to the variants of concern compared to older males. Antibody levels significantly declined in both older sexes 6 months post second dose but receiving a third dose replenished antibody response and eliminated sex, age, and frailty disparities. Taken together, these findings suggest that the third dose of mRNA vaccine is crucial to protect older adults from SARS-CoV-2 infection, particularly older frail males that may be more vulnerable.