A bivalent Neisseria meningitidis recombinant lipidated factor H binding protein vaccine in young adults: Results of a randomised, controlled, dose-escalation phase-1 trial

作者：Richmond P C^*; Nissen M D; Marshall H S; Lambert S B; Roberton D; Gruber W C; Jones T R; Arora A

来源：Vaccine, 2012, 30(43): 6163-6174.

DOI：10.1016/j.vaccine.2012.07.065

• Meningococcal vaccines
• Neisseria meningitidis serogroup B
• Bacterial outer membrane proteins
• Bactericidal antibodies
• Factor H binding protein

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 mu g 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 mu g dose levels, respectively, had seroprotective (%26gt;= 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 mu g dose levels.

• 出版日期2012-9-21