Safety and immunogenicity of a tetravalent meningococcal serogroups A, C, W-135 and Y conjugate vaccine in adolescents and adults

Abstract

The highest incidence of invasive meningococcal disease is in young children, with a second peak in adolescents/young adults. All five major disease-causing serogroups (A, B, C, W-135 and Y) have been described in Asia. Immunogenicity and safety of the investigational meningococcal ACWY-tetanus toxoid conjugate vaccine (ACWY-TT, GlaxoSmithKline Biologicals) was evaluated in healthy, meningococcal conjugate vaccine-naïve adolescents in the Philippines, India and Taiwan. 1025 adolescents were randomized (3:1) to receive one dose of ACWY-TT or tetravalent ACWY polysaccharide vaccine (Mencevax™, Men-PS). Serum bactericidal activity using rabbit complement (rSBA) was measured. Local and systemic adverse reactions were recorded for 4 days. Safety data were pooled with results from a second, similarly designed study in adults for evaluation of grade 3 systemic events. The pre-specified immunogenicity criterion for non-inferiority to Men-PS was met. One month post-vaccination, ≥85.4%-97.1% had a vaccine response (post-titre ≥1:8 in initially seronegative and ≥4-fold increase in seropositive), versus 78.0%-96.6% after Men-PS, against each vaccine serogroup. Exploratory comparisons showed statistically significantly higher post-vaccination rSBA geometric mean titres against all serogroups following ACWY-TT versus Men-PS. Exploratory analysis showed no statistically significant differences between groups in grade 3 general symptoms; however, the statistical criterion for non-inferiority between pooled treatment groups in terms of the ratio of incidences of grade 3 general symptoms was not demonstrated. No SAEs were related to vaccination. ACWY-TT was immunogenic in Asian adolescents with a reactogenicity profile that was clinically acceptable and similar to that of licensed Men-PS. The results of this study indicate that ACWY-TT could be used as a third conjugate vaccine in the protection of adolescents against meningococcal disease.

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.…”

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

“…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.…”

Meningococcal quadrivalent tetanus toxoid conjugate vaccine (MenACWY-TT, Nimenrix™): A review of its immunogenicity, safety, co-administration, and antibody persistence

“…Vaccine response was non-inferior to MenACWY PS and the post-vaccination rSBA GMT against all serogroups were statistically significantly higher following MenACWY-TT versus MenACWY-PS vaccine after one month. 54 Another study including 225 adolescents from Philippines and Saudi Arabia also showed noninferiority in the immunologic response to MenACWY-TT compared to the PS vaccine. 55 Berry et al studied the role of O-acetylation of serogroup APS antigenic epitopes in humans and mice and demonstrated that serum bactericidal titers following immunization with de-O-acetylated (de-O-Ac) conjugate vaccine were at least 32-fold lower than those following immunization with O-Ac PS-conjugate vaccine.…”