The immunogenicity and safety of an investigational meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine (ACWY-TT) compared with a licensed meningococcal tetravalent polysaccharide vaccine

Abstract

Immunogenicity and safety of ACWY-TT compared with licensed ACWY polysaccharide vaccine (MenPS) in healthy adults, and lot-to-lot consistency of three ACWY-TT lots were evaluated in a phase 3, open, controlled study. Adults aged 18–55 y were randomized to receive ACWY-TT (one of three lots) or MenPS. Serum bactericidal antibodies (rSBA) were measured pre- and 1 mo post-vaccination. Adverse events (AEs) were assessed 4 d (solicited symptoms) and 31 d (unsolicited symptoms) post-vaccination. Serious AEs were reported up to 6 mo after vaccination. The number of vaccinated subjects was 1247 (ACWY-TT, n = 935; MenPS, n = 312). ACWY-TT lot-to-lot consistency and non-inferiority of ACWY-TT as compared with MenPS groups were demonstrated according to pre-specified criteria. The percentages of subjects with a vaccine response (VR = rSBA titer ≥ 1:32 in initially seronegative; ≥ 4-fold increase in initially seropositive) to ACWY-TT vs. MenPS were 80.1%/69.8% (serogroup A), 91.5%/ 92.0% (C), 90.2%/85.5% (W-135), 87.0%/78.8% (Y). Exploratory analyses showed that for serogroups A, W-135 and Y, VR rates and GMTs were significantly higher for ACWY-TT compared with MenPS. For each serogroup, ≥ 98.0% of subjects had rSBA titers ≥ 1:128. Grade 3 solicited AEs were reported in ≤ 1.6% of subjects in any group. The immunogenicity of ACWY-TT vaccine was non-inferior to MenPS for all four serogroups in adults, with significantly higher VR rates to serogroups A, W-135 and Y and an acceptable safety profile. Consistency of 3 ACWY-TT production lots was demonstrated. These data suggest that, if licensed, ACWY-TT conjugate vaccine may be used for protection against invasive meningococcal disease in healthy adults. This study is registered at clinicaltrials.gov NCT00453986

Meningococcal Polysaccharide A O -Acetylation Levels Do Not Impact the Immunogenicity of the Quadrivalent Meningococcal Tetanus Toxoid Conjugate Vaccine: Results from a Randomized, Controlled Phase III Study of Healthy Adults Aged 18 to 25 Years

“…Exploratory analyses showed that the rSBA GMTs evaluated with both GlaxoSmithKline and HPA assays for meningococcal serogroups A, W-135, and Y were higher in subjects vaccinated with MenACWY-TT than in those who received the Men-PS vaccine. These results are consistent with those obtained previously for adults 18 to 55 years of age (36). Exploratory analysis done on the results obtained with the HPA assay showed that the percentages of subjects with rSBA titers of Ն1:8 for serogroups C and Y and with rSBA titers of Ն1:128 for serogroups A, W-135, and Y were statistically significantly higher among subjects vaccinated with the MenACWY-TT lot with the lowest level of O-acetylation of the meningococcal serogroup A PS than among those who received the Men-PS vaccine.…”

“…Pain at the injection site tended to be reported more frequently for participants who received the MenACWY-TT vaccine than the Men-PS vaccine. This observation is consistent with previous studies showing that injection site reactions are more frequent in individuals vaccinated with MenACWY-TT versus Men-PS (35,36,45,46) and those vaccinated with other quadrivalent meningococcal conjugate vaccines versus plain PS vaccines (47,48). It is likely that the increased reactogenicity following vaccination with the MenACWY-TT vaccine is due to the TT component (49).…”

“…High prevaccination rSBA titers have also been reported in other studies with meningococcal conjugate vaccines conducted with adults (36,38,39) and are consistent with the knowledge that immunity to meningococcal strains increases with age (40). It is likely that circulating meningococcal strains causing asymptomatic nasopharyngeal carriage and acquisition of functional antibodies due to natural immunity may contribute to these high observed seropositivity rates.…”

“…The safety profile of MenACWY-TT was comparable to that observed in previous studies conducted with adolescents and young adults (42,43). However, a lower incidence of pain at the injection site was observed in two other studies, one conducted with adolescents from India, Taiwan, and the Philippines (26.2%) (44) and the other with adults from Lebanon and the Philippines (19.4%) (36). It is possible that the lower incidence of pain observed in the two latter studies reflects cultural differences in the reporting of symptoms.…”

Randomized Clinical Trial To Evaluate the Immunogenicity of Quadrivalent Meningococcal Conjugate and Polysaccharide Vaccines in Adults in the United Kingdom

“…Similar results have also been demonstrated in studies conducted in Asia and continental Europe which compared a quadrivalent tetanus toxoid conjugate meningococcal vaccine and MenACWY-PS (16)(17)(18). The differences seen in the current study may relate to geographical variations in meningococcal nasopharyngeal carriage between the United Kingdom study population and those from previous studies leading to differential degrees of natural priming or may be due to differences in the comparator polysaccharide vaccine used.…”