SAN FRANCISCO, CA—Various investigational vaccine formulations against meningococcal serogroups A, B, C, W, and Y elicited similar responses in adolescents to those anticipated from the constituent ACWY and B vaccines, a study presented at IDWeek 2013 has found.
In 2005, the licensure of quadrivalent conjugate ACWY vaccines improved the breadth of protection against meningococcal meningitis and sepsis; however, global control of this disease would be more effective with all five vaccine-preventable serogroups in one vaccine, reported Xavier Saez-Llorens, MD, from Hospital del Niño, Panama City, Panama, and colleagues in explaining the rationale for their Phase 2 to examine novel formulations of ABCWY vaccines in adolescents.
The multicenter, observer-blind, controlled study included 495 (1 unvaccinated) healthy adolescents 11–18 years of age randomized to six study groups. The vaccines comprised recombinant proteins (rMenB) and outer membrane vesicles (OMV) components of a European-approved serogroup B vaccine with a licensed quadrivalent polysaccharide-protein conjugate ACWY vaccine. Two doses of each vaccine formulation were administered, at 0 and 2 months.
Patients in Group I (n=81) received MenACWY + rMenB (1x); Group II (n=81), MenACWY + rMenB (2x); Group III (n=83), MenACWY + rMenB (1x) + OMV (1x); Group IV (n=82), MenACWY + rMenB (1x) + OMV (1/4x); Group V (n=85), rMenB (1x); and Group VI (n=82), MenACWY at 0 month, and placebo at 2 months.
The investigators measured serum bactericidal activities with human complement (hSBA) prior to and 1 month after each vaccination. Adverse events were assessed throughout the study duration.
Results showed that bactericidal antibodies against two recombinant serogroup B antigen components (fHbp, NadA) in Groups I-V were increased after one dose of rMenB, with 100% of subjects achieving an hSBA titer ≥5 after the second dose, with further increases in GMTs than after the first dose.
“As expected, only Groups III and IV displayed significant responses to OMV, 78% and 71%, respectively,” Dr. Saez-Llorens reported.
Bactericidal antibodies against serogroups ACWY were increased in Groups I-IV after a single dose and were similar to those in the ACWY Group A (86%), C (68%), W (60%), and Y (78%). A second dose in Groups I–IV elicited higher response rates for A (97−98%), C (95−97%), W (74−86%) and Y (92%−96%). Two doses of rMenB alone (Group V), elicited bactericidal responses against non-B serogroups; that is, reference strains for serogroups A (87%), C (29%), and W (47%).
Results regarding safety showed rate of local reactions were higher in Groups I–IV (range 84–90%) than Groups V (80%) or VI (60%) after one dose. However, after the second dose, the rate was similar (range 65–84%). In the case of systemic reactions, primarily myalgia and headache were reported after Dose 1 (62–76%) and Dose 2 (46−59%), respectively, in Groups I–V, and 55% and 56% in Group VI. There were no vaccine-related serious adverse events.
“Only formulations that included OMV resulted in a robust immune response against the outer membrane protein PorA (NZ98/254 reference strain),” Dr. Saez-Llorens noted.
Participants in all six groups displayed “generally acceptable tolerability” and the various A, B, C, W, Y formulations resulted in similar seroresponse rates to the constituent ACWY and B vaccines, he concluded.