Frailty impacts immune responses to Moderna COVID-19 mRNA vaccine in older adults

Background Immune responses to COVID-19 mRNA vaccines have not been well characterized in frail older adults. We postulated that frailty is associated with impaired antibody and cellular mRNA vaccine responses. Methods We followed older adults in a retirement facility with longitudinal clinical and serological samples from the first Moderna mRNA-1273 vaccine dose starting in February 2021 through their 3rd (booster) vaccine dose . Outcomes were antibody titers, antibody avidity, and AIM+ T cell function and phenotype. Statistical analysis used linear regression with clustered error for antibody titers over multiple timepoints with clinical predictors including, age, sex, prior infection status, and clinical frailty scale (CFS) score. T cell function analysis used linear regression models with clinical predictors and cellular memory phenotype variables. Results Participants ( n = 15) had median age of 90 years and mild, moderate, or severe frailty scores ( n = 3, 7, or 5 respectively). Over the study time course, anti-spike antibody titers were 10-fold higher in individuals with lower frailty status ( p = 0.001 and p = 0.005, unadjusted and adjusted for prior COVID-19 infection). Following the booster, titers to spike protein improved regardless of COVID-19 infection or degree of frailty ( p = 0.82 and p = 0.29, respectively). Antibody avidity significantly declined over 6 months in all participants following 2 vaccine doses ( p < 0.001), which was further impaired with higher frailty ( p = 0.001). Notably, avidity increased to peak levels after the booster ( p < 0.001). Overall antibody response was inversely correlated with a phenotype of immune-senescent T cells, CD8 + CD28- TEMRA cells ( p = 0.036, adjusted for COVID-19 infection). Furthermore, there was increased detection of CD8 + CD28- TEMRA cells in individuals with greater frailty ( p = 0.056, adjusted for COVID-19). Conclusions We evaluated the immune responses to the Moderna COVID-19 mRNA vaccine in frail older adults in a retirement community. A higher degree of frailty was associated with diminished antibody quantity and quality. However, a booster vaccine dose at 6 months overcame these effects. Frailty was associated with an increased immune-senescence phenotype that may contribute to the observed changes in the vaccine response. While the strength of our conclusions was limited by a small cohort, these results are important for guiding further investigation of vaccine responses in frail older adults.