Authors:
Richmond, P. C.; Nissen, M. D.; Marshall, H. S.; Lambert, S. B.; Roberton, D.; Gruber, W. C.; Jones, T. R.; Arora, A.
Authors notes:
Keywords:
Bacterial outer membrane proteins, Bactericidal antibodies, Factor H binding protein, Meningococcal vaccines, Neisseria meningitidis serogroup B
Abstract
Neisseria meningitidis is a leading cause of meningitis and septicaemia, but a broadly-protective vaccine against endemic serogroup B disease is not licensed and available.
The conserved, outer-membrane lipoprotein factor H binding protein (fHBP, also known as LP2086) is expressed as one of two subfamily variants in virtually all meningococci.
This study investigated the safety, tolerability, and immunogenicity of a recombinant-expressed bivalent fHBP (r-fHBP) vaccine in healthy adults.
Participants (N= 103) aged 18-25 years were recruited into three ascending dose level cohorts of 20, 60, and 200. μg of a bivalent r-fHBP vaccine formulation and randomised to receive vaccine or placebo at 0, 1, and 6 months.
The vaccine was well tolerated. Geometric mean titres (GMTs) for r-fHBP subfamily-specific IgG antibodies increased 19-168-fold from pre-vaccination to post-dose 2 in a dose level-dependent manner. In addition, robust serum bactericidal assay using human complement (hSBA) responses for strains expressing both homologous and heterologous fHBP variants were observed.
After three vaccinations, 16-52% of the placebo group and 47-90%, 75-100%, and 88-100%, of the 20, 60, and 200. μg dose levels, respectively, had seroprotective (≥1:4) hSBA titres against six serogroup B strains.
The bivalent r-fHBP vaccine was well tolerated and induced robust bactericidal activity against six diverse serogroup B strains in young adults at the 60 and 200. μg dose levels.