The first use of an investigational multicomponent meningococcal serogroup B vaccine (4CMenB) in humans
Volume 7, Issue 6
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Pages 646 - 653http://dx.doi.org/10.4161/hv.7.6.15482
Authors: Daniela Toneatto, Shevqet Ismaili, Ellen Ypma, Kay Vienken, Philipp Oster and Peter Dull View affiliations
Background: Neisseria meningitidis serogroup B is a well-recognized cause of bacterial meningitis and sepsis for which no broadly protective vaccine exists. Whole genome sequencing was used to identify three antigens: factor H binding protein (fHbp), Neisserial adhesin A (NadA), and Neisseria heparin binding antigen (NHBA) for an investigational vaccine candidate (rMenB). This was the first trial of an investigational multicomponent meningococcal serogroup B vaccine (4CMenB), containing rMenB and outer membrane vesicles (OMV) from the New Zealand epidemic strain in humans. Results: Seventy adults enrolled and received study vaccine. All vaccines were generally well tolerated. Immune responses were observed to multiple serogroup B strains following all investigational vaccines, suggesting the potential for broad coverage against this serogroup. Immunogenicity was enhanced by the addition of OMV; the 4CMenB displayed the optimal profile for further investigation. Methods: In a phase I, observer blind, randomized trial, healthy adults (18-40 years of age) were randomized 2:2:1 to receive 3 doses of 4CMenB, rMenB with OMV from the Norwegian outbreak strain, or rMenB alone. Pre- and postvaccination sera were evaluated in a serum bactericidal assay using human complement (hSBA) against a panel of 15 serogroup B strains, with titers ≥4 considered protective. Solicited injection site and systemic reactions were evaluated for 7 days following each vaccination and adverse events were reported throughout the study. Conclusion: In this trial, 4CMenB displayed a favorable profile for further clinical development. 4CMenB demonstrated immunogenicity against multiple heterologous serogroup B strains. All vaccines were generally well tolerated in this study.
Received: October 21, 2010; Accepted: March 11, 2011