Sustained salivary IgG but short-lived IgA responses following primary and booster MenACWY-TT vaccination in older adults

Carriage of <i>Neisseria meningitidis</i> is essential in meningococcal transmission and is a prerequisite for invasive meningococcal disease (IMD). Meningococcal conjugate vaccines have been suggested to reduce acquisition of carriage in adolescents and young adults, contributing to herd protection. Mucosal immunity is considered key in protection against colonization. While mucosal antibody responses following parenteral meningococcal conjugate vaccination have been described in infants, adolescents and young adults, data in older adults, who are at increased risk for infectious diseases including IMD, are limited. This phase IV, open-label clinical trial (CTIS: 2024-513640-29-00) assessed antibody responses in saliva in 216 adults aged 65-85 y following primary meningococcal serogroup A, C, W, and Y conjugate vaccine (MenACWY-TT) vaccination. A booster dose was administered 1 y later in a sub-cohort (n = 100). MenACWY polysaccharide (ps)-specific IgA and IgG concentrations were measured in paired saliva and serum. Primary MenACWY-TT vaccination significantly increased salivary IgA and IgG concentrations for all serogroups. Salivary IgA concentrations returned to baseline within 1-2 y, whereas IgG concentrations remained elevated for at least 2 y. Booster vaccination enhanced salivary IgG concentrations, but failed to boost salivary IgA responses. Strong correlations were observed between post-vaccination salivary and serum IgG concentrations, and between salivary IgA and secretory component levels, suggesting systemic origin of IgG and mucosal origin of IgA. These findings highlight that MenACWY-TT vaccination induces durable salivary IgG and transient IgA responses in older adults, with limited enhancement of mucosal IgA after booster vaccination.