Novel Intervention in the Aging Population: A Primary Meningococcal Vaccine Inducing Protective IgM Responses in Middle-Aged Adults

Marieke Van Der Heiden,Axel A Bonacic Marinovic,Irina Tcherniaeva,Anne-Marie Buisman,Marjan Van Maurik,Lia G H De Rond,Annemieke M H Boots,Guy A M Berbers

doi:10.3389/fimmu.2017.00817

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.

Highlights

To assess the duration of protection, we focused on the predicted percentages of participants that possessed an rSBA titer >8 and >128, for any given time up to 10 years post-vaccination
We demonstrate that a primary tetravalent meningococcal vaccine conjugated to tetanus toxoid (TT) (MenACWY-TT) in middle-aged adults is highly immunogenic
1 year post-vaccination protective antibody titers were still found in 76–94% of the participants

Summary

Introduction

Population aging has major medical implications, as with age vulnerability to both chronic and infectious diseases increases. Due to increased numbers of susceptible elderly, the population herd immunity against infectious diseases may diminish [2, 3]. With age, reduced thymic output of naïve T-cells and reduced bone marrow B-cell niches are observed, causing compositional changes in both compartments of the adaptive immune system [5–8]. These alterations affect both the cellular and the humoral immune responses to vaccines [7, 9]. Larger effects of immunological aging are expected for de novo immune responses, as compared with the above-mentioned recall responses (hereafter called booster responses), due to reduced numbers of naïve cells [2, 3, 16]

Methods

Results

Conclusion