Different Long-Term Duration of Seroprotection against Neisseria meningitidis in Adolescents and Middle-Aged Adults after a Single Meningococcal ACWY Conjugate Vaccination in The Netherlands

Abstract

Neisseria meningitidis is often asymptomatically carried in the nasopharynx but may cause invasive meningococcal disease, leading to morbidity and mortality. Meningococcal conjugate vaccinations induce functional protective antibodies against capsular antigens, but seroprotection wanes over time. We measured functional antibody titers five years after administration of a single dose of the meningococcal ACWY-polysaccharide-specific tetanus toxoid-conjugated (MenACWY-TT) vaccine in adolescents and middle-aged adults in the Netherlands, using the serum bactericidal antibody with baby rabbit complement (rSBA) assay. Protection was defined as rSBA titer ≥8. The meningococcal ACWY-specific serum IgG concentrations were measured with a multiplex immunoassay. Duration of protection was estimated by a bi-exponential decay model. Sufficient protection for MenC, MenW, and MenY was achieved in 94–96% of the adolescents five years postvaccination, but, in middle-aged adults, only in 32% for MenC, 65% for MenW and 71% for MenY. Median duration of protection for MenCWY was 4, 14, and 21 years, respectively, in middle-aged adults, while, in adolescents, it was 32, 98, and 33 years. Our findings suggest that adolescents, primed in early childhood with MenC conjugate vaccination, remain sufficiently protected after a single dose of MenACWY-TT vaccine. Middle-aged adults without priming vaccination show fast waning of antibodies, particularly MenC, for which protection is lost after four years.

Meningococcal vaccination in adolescents and adults induces bactericidal activity against hyperinvasive complement-resistant meningococcal isolates

“…Additionally tested cc11 MenW isolates showed comparable titers in a subset of participants (Supplementary Table 3). The waning of long-term seroprotection after MenACWY vaccination is different between these age groups, as was previously studied in those individuals as part of a larger cohort (23).…”

“…The serum bactericidal antibody (SBA) assay was performed using pooled serum as well as individual sera and baby rabbit complement as complement source (20, 21). The serum pools consisted of sera from 1) unvaccinated adults and 2) adolescents and young adults five years after a single dose of the MenACWY-TT vaccine (Supplementary Table 2) (22, 23). We determined the resistance to killing of invasive and carriage isolates in the absence (serum pool 1) and presence (serum pool 2) of vaccine-induced antibodies.…”

“…Additionally, we tested a randomly selected subset (n=22) of sera from the adolescent cohort to determine the SBA titer against three additional serogroup W cc11 isolates to explore the variation in resistance to killing among different isolates belonging to this specific cc (isolate #30, isolate #35, isolate #49; Supplementary Table 1 and 3). The internationally accepted correlate of protection (SBA titer ≥8) was used for analysis of the individual sera, with the bactericidal titer defined as the dilution of sera that yielded ≥50% killing after 60 minutes incubation (23)(24)(25). A value of 2 was assigned when the titer fell below the cut-off of the assay (titer <4).…”

“…The individual sera from adolescents (n=54) and middle-aged adults (n=50) were collected five years after a single dose of MenACWY-TT in two clinical studies (NL4518 and NL7735) (23). The sera were tested with the default MenW non-cc11 target isolate (cc22, strain MP01240070) and the default MenW cc11 target isolate (2160326) used in our laboratory for SBA assays.…”

A novel vaccine to prevent meningococcal disease beyond the first year of life: an early review of MenACYW-TT

“…These studies will provide extensive data on the safety and immunogenicity of this vaccine versus locally licensed meningococcal vaccines and on its compatibility with other routine pediatric vaccines in the respective NIPs, including meningococcal serogroup B vaccine in the UK. Interestingly, priming the immune system early in childhood may confer the benefit of an enhanced duration of protection [112]. In toddlers, study MEQ00065 (EudraCT: 2018-003790-10) is assessing the superiority of the serogroup C response versus Meningococcal Group C-TT Conjugate Vaccine, Adsorbed (MenC-TT; NeisVac-C ® , Pfizer), with preliminary results suggesting that MenACYW-TT elicits statistically superior serogroup C responses (as measured by hSBA and rSBA seroprotection rates and GMTs) compared with both MCV4-TT and MenC-TT [113].…”