Persistence of the immune response after MenACWY-CRM vaccination and response to a booster dose, in adolescents, children and infants

Abstract

Persistence of bactericidal antibodies following vaccination is extremely important for protection against invasive meningococcal disease, given the epidemiology and rapid progression of meningococcal infection. We present an analysis of antibody persistence and booster response to MenACWY-CRM, in adolescents, children and infants, from 7 clinical studies. Immunogenicity was assessed using the serum bactericidal assay with both human and rabbit complement. Post-vaccination hSBA titers were high, with an age-and serogroup-specific decline in titers up to 1 y and stable levels up to 5 y The waning of hSBA titers over time was more pronounced among infants and toddlers and the greatest for serogroup A. However, rSBA titers against serogroup A were consistently higher and showed little decline over time, suggesting that protection against this serogroup may be sustained. A single booster dose of MenACWY-CRM administered at 3 to 5 y induced a robust immune response in all age groups.

Protecting the most vulnerable age group: a review of MenACWY-TT immunogenicity and safety in infants

“…Serogroup C GMTs were also generally higher when measured in hSBA compared with rSBA, but the opposite tended to be true after a single primary dose [28][29][30][31]. Although it is well established that hSBA and rSBA results often do not coincide [38,39], these discordant results have been noted by others, particularly regarding serogroup A [40]; similar results have been observed for other meningococcal conjugate vaccines targeting serogroup A [41][42][43]. These findings, coupled with serogroup C rSBA titers ≥1:8 being established as the correlate of protection based on effectiveness studies [35,44], have fueled the argument that rSBA titers are more clinically relevant for MenACWY-TT immunogenicity evaluations than hSBA titers [40].…”

“…The lower persistence for serogroup A appears to be a class effect of all MenACWY conjugate vaccines, particularly when using the hSBA assay. Accordingly, the percentages of subjects with hSBA titers ≥1:8 following vaccination with MenACWY-CRM 197 at 6-8 and 12 months of age declined by 7 months after the last dose to 31% for serogroup A compared with >70% for other serogroups [41]. Low persistence of serogroup A antibody responses relative to antibody responses for serogroups C, W, and Y has also been reported following primary vaccination with MenACWY-CRM 197 and MenACWY-D in adolescents [42], although persistence data for MenACWY-D were not available in infants.…”

An update of clinical experience with the quadrivalent meningococcal ACWY-CRM conjugate vaccine

“…Priming, persistence, and booster data show that MenACWY-CRM is immunogenic in all the populations and age-groups evaluated, regardless of country of origin, and induces both long-term persistence and immunological memory, and a robust, anamnestic and early booster response. The somewhat lower immunogenicity and shorter persistence of antibodies to the serogroup A polysaccharide compared with the other vaccine serogroups has been observed for all quadrivalent meningococcal conjugate vaccines containing serogroup A, especially when tested using hSBA [32,50,62,63]. The similarity of the observations suggests that the rapid decrease in hSBA titers for serogroup A is likely to be an antigen-specific feature rather than a vaccine-specific feature.…”

“…HBV: hepatitis B vaccine; PCV7/13: 7/13-valent pneumococcal conjugate vaccine; MMR/V: measles-mumps-rubella (varicella) vaccine; DTaP: combined diphtheria-tetanus-acellular pertussis vaccine; IPV: inactivated poliovirus vaccine; Hib: Haemophilus influenzae type b conjugate vaccine; GMT: geometric mean titer. antibodies after MenACWY-CRM vaccination in different age groups has been recently reviewed by Baxter et al [32]. Booster vaccination at 5 years of age induced large increases in hSBA titers of 42-113-fold for all serogroups, with titers that were higher than after the fourth dose at 12 months, indicating persistence of immune memory until at least 5 years of age.…”

Immunogenicity and safety of a booster dose of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) in adolescents and adults: a Phase III randomized study

“…Immunity following vaccination with MCV4 may wane over time; in a case-controlled surveillance study of MCV4-DT recipients in the USA vaccine effectiveness was 79% (95% CI 49-91%) for adolescents vaccinated <1 y before, 69% (95% CI 44, 83%) for adolescents vaccinated 1 to <3 y before, and 61% (95% CI 25, 79%) for adolescents vaccinated 3 to <8 y before. 17 The waning of hSBA titers has also been demonstrated following vaccination with MCV4-CRM, 18 which led to the recommendation by ACIP in the US for a booster dose at 16 y. 19 For the same reason, in countries such as the UK, the Netherlands, and Australia, which have different recommended vaccines and schedules, booster vaccinations have been found to be effective in populations considered to be at higher risk of infection.…”