Association of frailty, age, and biological sex with SARS-CoV-2 mRNA vaccine-induced immunity in older adults

Abstract

Background: Male sex and old age are risk factors for severe COVID-19, but the intersection of sex and aging on antibody responses to SARS-CoV-2 vaccines has not been characterized. Methods: Plasma samples were collected from older adults (75-98 years) before and after three doses of SARS-CoV-2 mRNA vaccination, and from younger adults (18-74 years) post-dose two, for comparison. Antibody binding to SARS-CoV-2 antigens (spike protein [S], S-receptor binding domain [S-RBD], and nucleocapsid [N]) and functional activity against S were measured against the vaccine virus and variants of concern (VOC). Results: Vaccination induced greater antibody titers in older females than males, with both age and frailty associated with reduced antibody responses to vaccine antigens in males, but not females. ACE2 binding inhibition declined more than anti-S or anti-S-RBD IgG in the six months following the second dose (28-fold vs. 12- and 11-fold decreases in titer). The third dose restored functional antibody responses and eliminated disparities caused by sex, age, and frailty in older adults. Responses to the VOC were significantly reduced relative to the vaccine virus, with older males having lower titers to the VOC than females. Older adults had lower responses to the vaccine and VOC viruses than younger adults, with disparities being greater in males than females. Conclusion: Older and frail males may be more vulnerable to breakthrough infections due to low antibody responses before receipt of a third vaccine dose. Promoting third dose coverage in older adults, especially males, is crucial to protecting this vulnerable population.

Safety and immunogenicity of inactivated SARS-CoV-2 vaccines in people with gastrointestinal cancer

“…Their B and T cells are less responsive to outside stimuli. They are more likely to have a severe course of COVID-19 and are associated with higher mortality (Bubar et al, 2021;Ramasamy et al, 2021;Shapiro et al, 2022). Previous studies have also reported that patients aged >65 years had significantly lower serum antibody titers after vaccination (Ariamanesh et al, 2022;Erdogan et al, 2022).…”

Shedding of Infectious SARS-CoV-2 Despite Vaccination

“…Age and male sex have been considered risk factors for COVID-19 disease [22][23][24][25][26]. While one might hypothesize that older individuals and/or males might have higher SARS-CoV-2 burdens and therefore lower Ct values at the time of testing, evidence for this is mixed, with some studies reporting lower Ct values in older individuals [24,27], others in younger individuals [28], and still others finding no difference by age [20,[29][30][31][32][33][34].…”

Memory CD8+ T cell diversity and B cell responses correlate with protection against SARS-CoV-2 following mRNA vaccination

“…Little is known about how sex may impact the immunogenicity and protection elicited by mRNA vaccine. Ageand frailty-associated decrease in humoral responses is greater in males than in females 49 . The age-related decreases in antibody titers observed in males have been also associated with a decline in CD4 + T cell responses 50 .…”