Santolaya ME, O’Ryan M, Valenzuela MT, Prado V, Vergara R, Muñoz A, Grana MG, Wang H, Kimura A, Dull P, Toneatto D
Whole genome sequencing was used to identify three of four major protein components of an investigational multicomponent meningococcal vaccine (4CMenB).
In an observer-blind study in Santiago, Chile, 11-17-year-old adolescents were randomized to receive 1-3 doses of 4CMenB or placebo at baseline, one and/or two months later. Primary immunogenicity outcome was a titer ≥4 in a serum bactericidal assay using human complement (hSBA) against three test strains selected to evaluate the contribution of individual vaccine antigens. Tolerability was assessed by solicited local and systemic reactions within seven days of each study vaccination. Adverse events were monitored throughout the study.
Overall, 1631 adolescents (56% female; mean age 13.8 ± 1.9 years) received 4CMenB and/or placebo. One month later 92–97% of recipients of one 4CMenB dose, 99–100% after 2 or 3 4CMenB doses and 29–50% of placebo recipients had hSBA titers ≥4 against the three test strains. Similar proportions of placebo and 4CMenB recipients reported solicited local (89–94%) and systemic (70–79%) reactions after the first study injection. At subsequent visits, reports of reactogenicity were less frequent in all groups, but placebo recipients were less likely to report reactogenicity outcomes than 4CMenB recipients.
4CMenB induced robust immune responses and had an acceptable tolerability profile following one, two, or three doses and all schedules administered. Three doses of 4CMenB imparted no additional benefits compared with two doses. No evidence of increased reactogenicity was observed with 2 or 3 doses compared with one dose of 4CMenB.