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

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dc.contributor.authorRichmond, P.
dc.contributor.authorNissen, M.
dc.contributor.authorMarshall, H.
dc.contributor.authorLambert, S.
dc.contributor.authorRoberton, D.
dc.contributor.authorGruber, W.
dc.contributor.authorJones, T.
dc.contributor.authorArora, A.
dc.date.issued2012
dc.description.abstractNeisseria 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 200μg 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 200μg 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 200μg dose levels.
dc.description.statementofresponsibilityP.C. Richmond, M.D. Nissen, H.S. Marshall, S.B. Lambert, D. Roberton, W.C. Gruber, T.R. Jones and A. Arora
dc.identifier.citationVaccine, 2012; 30(43):6163-6174
dc.identifier.doi10.1016/j.vaccine.2012.07.065
dc.identifier.issn0264-410X
dc.identifier.issn0264-410X
dc.identifier.orcidMarshall, H. [0000-0003-2521-5166]
dc.identifier.urihttp://hdl.handle.net/2440/73741
dc.language.isoen
dc.publisherElsevier Sci Ltd
dc.rights© 2012 Elsevier Ltd.
dc.source.urihttps://doi.org/10.1016/j.vaccine.2012.07.065
dc.subjectHumans
dc.subjectNeisseria meningitidis, Serogroup B
dc.subjectMeningococcal Infections
dc.subjectBacterial Proteins
dc.subjectImmunoglobulin G
dc.subjectVaccines, Synthetic
dc.subjectMeningococcal Vaccines
dc.subjectAntibodies, Bacterial
dc.subjectAntigens, Bacterial
dc.subjectDouble-Blind Method
dc.subjectAdult
dc.subjectComplement System Proteins
dc.subjectFemale
dc.subjectMale
dc.subjectYoung Adult
dc.subjectSerum Bactericidal Antibody Assay
dc.titleA bivalent Neisserie meningitidis recombinant lipidated factor H binding protein vaccine in young adults: results of a randomised, controlled, dose-escalation phase 1 trial
dc.typeJournal article
pubs.publication-statusPublished

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