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

Abstract

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.

COVID-19 adenoviral vector vaccination elicits a robust memory B cell response with the capacity to recognize Omicron BA.2 and BA.5 variants

“…Others have also found differences in SARS-CoV-2-specific antibody quantities across age groups, and together this supports the implementation of separate vaccination schedules for more highrisk groups such as the elderly, to boost protective IgG and Bmem levels. [89][90][91][92] The third COVID-19 vaccine dose has been shown to significantly boost NAb levels against Omicron, regardless of the primary vaccine formulation. 93 It will be of interest to also examine RBD-specific Bmem recognition of VoC after booster doses, as these memory cells will likely be the source of these increased NAb titers.…”

Antibody response in elderly vaccinated four times with an mRNA anti-COVID-19 vaccine

“…Finally, we did not find any influence of frailty on anti-RBD IgG or nAb levels but this is limited by the absence of severely frail participants in the studied population. Nonetheless, another study indicated that the booster vaccination appeared to overcome the effects of frailty on spike and RBD protein antibody quantity for severely frail individuals 37 .…”

Immune response kinetics to SARS-CoV-2 infection and COVID-19 vaccination among nursing home residents—Georgia, October 2020–July 2022

“…The decay in antibodies and MBCs observed in our cohorts of nursing home residents may be attributed to immunosenescence [ 41 ]. Published studies have also indicated frailty, defined as a complex phenomenon due to a cumulative decline in multiple physiologic systems resulting in reduced resistance to stressors, as an explanation for decreased post-vaccine antibody response [ 6 , 42 , 43 ], where higher levels of frailty result in decreased SARS-CoV-2 antibody responses, similar to what has been observed following the receipt of other viral vaccines (e.g., Zoster [ 44 ]). A study by Shapiro et al indicated that immune response to a third dose of mRNA COVID-19 vaccine booster dose appears to overcome reduced immunity associated with frailty [ 45 ], consistent with our findings, based on linear mixed modeling, indicating reduced decay rates after multiple spike exposures.…”