Early humoral and cellular responses after bivalent SARS‐CoV‐2 mRNA‐1273.214 vaccination in long‐term care and retirement home residents in Ontario, Canada: An observational cohort study

Abstract

AbstractImmunogenicity of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) bivalent mRNA‐1273.214 vaccine (Original/Omicron B.1.1.529 [BA.1]) is underreported in vulnerable older adults in congregate care settings. In residents of 26 long‐term care and retirement homes in Ontario, Canada, humoral (i.e., serum anti‐spike and anti‐receptor binding domain [anti‐RBD]) IgG and IgA antibodies and live SARS‐CoV‐2 neutralization) and cellular (i.e., CD4+ and CD8+ activation‐induced marker spike‐specific T cell memory) responses were assessed 7–120 days postvaccination with four monovalent mRNA vaccines (n = 494) or subsequent bivalent mRNA‐1273.214 vaccination (fifth vaccine) (n = 557). Within 4 months, anti‐spike and anti‐RBD antibody levels were similar after monovalent and bivalent vaccination in infection‐naïve individuals. Hybrid immunity (i.e., vaccination and natural infection) generally increased humoral responses. After bivalent vaccination, compared to monovalent vaccination, residents with hybrid immunity had elevated anti‐spike and anti‐RBD IgG and IgA antibodies. Omicron BA.1 antibody‐mediated neutralization, and CD8+ T cell memory responses to the Omicron BA.1 spike protein, were also higher after bivalent vaccination. Humoral and cellular responses were, therefore, noninferior within 4 months of bivalent mRNA‐1273.214 vaccination compared to monovalent mRNA vaccination. Waning of humoral but not cellular immunity was particularly evident in individuals without hybrid immunity. Continued monitoring of vaccine‐associated and hybrid immunity against emerging Omicron variants of concern is necessary to assess longevity of protection.