ABSTRACT: Vaccine responses are often reduced in the elderly, leaving part of the elderly population vulnerable to infectious diseases. Timely vaccination may offer a solution for strengthening memory immunity before reaching old age, which classifies middle-aged persons as a target age group for vaccine interventions. However, knowledge regarding the immunogenicity of primary immunizations in middle-aged adults is lacking. We determined the immunogenicity of a primary meningococcal vaccine towards which no or (very) low pre-vaccination immunity exists in middle-aged adults (NTR4636).A vaccine containing multiple meningococcal groups (tetravalent) conjugated to tetanus toxoid (MenACWY-TT) was administered to middle-aged adults (50-65?years of age, N?=?204) in a phase IV single-center and open-label study. Blood samples were taken pre-, 7?days, 28?days, and 1?year post-vaccination. Functional antibody titers were measured with the serum bactericidal assay (SBA). Meningococcal- and tetanus-specific antibody responses were determined with a fluorescent bead-based multiplex immunoassay. A bi-exponential decay model was used to estimate long-term protection.In the majority of the participants, the meningococcal vaccine clearly induced naïve responses to meningococci W (MenW) and meningococci Y (MenY) as compared to a booster response to meningococci C (MenC). After 28?days, 94, 99, and 97% of the participants possessed a protective SBA titer for MenC, MenW, and MenY, respectively, which was maintained in 76, 94, and 86% 1?year post-vaccination. At this 1-year time point, significantly lower SBA titers were found in participants without a pre-vaccination SBA titer. Overall, protective antibody titers were predicted to persist after 10?years in 40-60% of the participants. The SBA titers correlated well with the meningococcal-specific IgM responses, especially for MenW and MenY. Interestingly, these IgM responses were negatively correlated with age.Primary immunization with a tetravalent meningococcal vaccine was highly immunogenic in middle-aged adults, inducing protective antibody titers in the vast majority of the participants lasting for at least 1?year. The age-related decrease in highly functional IgM responses argues in favor of vaccination against de novo antigens before reaching old age and, hence, middle-aged persons are an age group of interest for future vaccine interventions to protect the aging population.
