Open AccessPhase I Safety and Immunogenicity Study of a Candidate Meningococcal Disease Vaccine Based on Neisseria lactamica Outer Membrane Vesicles
Author(s) -
Andrew Gorringe,
Stephen Taylor,
Charlotte Brookes,
Mary Matheson,
Michelle Finney,
Moyra Kerr,
Michael J. Hudson,
Jamie Findlow,
Raymond Borrow,
Nicholas Andrews,
George Kafatos,
Cariad Evans,
Robert C. Read
Publication year - 2009
Publication title -
clinical and vaccine immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.649
H-Index - 77
eISSN - 1556-6811
pISSN - 1556-679X
DOI - 10.1128/cvi.00118-09
Subject(s) - neisseria meningitidis , immunogenicity , meningococcal disease , meningococcal vaccine , microbiology and biotechnology , neisseria , virology , neisseriaceae , immunity , antibody , immune system , biology , medicine , immunology , immunization , antibiotics , bacteria , genetics
Natural immunity to meningococcal disease in young children is associated epidemiologically with carriage of commensalNeisseria species, includingNeisseria lactamica . We have previously demonstrated that outer membrane vesicles (OMVs) fromN. lactamica provide protection against lethal challenge in a mouse model of meningococcal septicemia. We evaluated the safety and immunogenicity of anN. lactamica OMV vaccine in a phase I placebo-controlled, double-blinded clinical trial. Ninety-seven healthy young adult male volunteers were randomized to receive three doses of either an OMV vaccine or an Alhydrogel control. Subsequently, some subjects who had received the OMV vaccine also received a fourth dose of OMV vaccine, 6 months after the third dose. Injection site reactions were more frequent in the OMV-receiving group, but all reactions were mild or moderate in intensity. The OMV vaccine was immunogenic, eliciting rises in titers of immunoglobulin G (IgG) against the vaccine OMVs, together with a significant booster response, as determined by an enzyme-linked immunosorbent assay. Additionally, the vaccine induced modest cross-reactive immunity to six diverse strains of serogroup BNeisseria meningitidis , including IgG against meningococcal OMVs, serum bactericidal antibodies, and opsonophagocytic activity. The percentages of subjects showing ≥4-fold rises in bactericidal antibody titer obtained were similar to those previously reported for the Norwegian meningococcal OMV vaccine against the same heterologous meningococcal strain panel. In conclusion, thisN. lactamica OMV vaccine is safe and induces a weak but broad humoral immune response toN. meningitidis .