Phase II/III randomized immunogenicity and safety study of a Brazilian meningococcal serogroup B vaccine in children

Abstract

From May 16, 2011 to March 13, 2013, Bio-Manguinhos/Fiocruz conducted a randomized Phase II/III study of a vaccine against N. menigitidis serogroup B, involving 280 children aged between 4 and 11 years, evaluating immunogenicity and safety. This was a dose-escalation study evaluating vaccine candidates containing 12.5 μg, 25 μg, and 50 μg of OMV protein per dose, with dLOS administered at half the concentration of the total protein. The VAMENGOC-BC® vaccine was used as a reference. The vaccination schedule included three doses administered two months apart, followed by a booster dose 6–12 months after the third injection. Bactericidal antibody responses were evaluated using the vaccine strains as primary targets and heterologous strains as secondary targets. All vaccines were well tolerated, and only for fever after the first dose there was a statistically significant difference across comparison groups (p = 0,007). Additionally, unsolicited adverse events and serious adverse events were determined not to be causally related to the vaccines. The candidate vaccines elicited a significant increase in total IgG antibodies against the OMV components of the first prevalent strain and achieved high bactericidal titers against both vaccine strains following the immunization schedule. After the booster dose, all children receiving either the experimental or the reference vaccine were protected against the vaccine strains. For heterologous strains, a protective response was observed based on the similarity of PorA, although the antibody levels remained low. Moreover, the inclusion of detoxified LOS in the experimental formulations underscores the need for further investigation into this molecule as a vaccine component, given that the observed response appears to be concentration dependent. The experimental vaccines showed immunogenicity equivalent to VA-MENGOC-BC® with formulations containing two to four times fewer protein components than the reference vaccine.