Phase I safety and immunogenicity study of a candidate meningococcal disease vaccine based on Neisseria lactamica outer membrane vesicles.
Natural immunity to meningococcal disease in young children is associated epidemiologically with carriage of commensal Neisseria species, including Neisseria lactamica. We have previously demonstrated that outer membrane vesicles (OMVs) from N. lactamica provide protection against lethal challenge in a mouse model of meningococcal septicemia. We evaluated the safety and immunogenicity of an N. 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 B Neisseria meningitidis, including IgG against meningococcal OMVs, serum bactericidal antibodies, and opsonophagocytic activity. The percentages of subjects showing > or =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, this N. lactamica OMV vaccine is safe and induces a weak but broad humoral immune response to N. meningitidis.
Gorringe
Andrew R
AR
Health Protection Agency, Centre for Emergency Preparedness and Response, Porton Down, Salisbury, UK. andrew.gorringe@hpa.org.uk
Taylor
Stephen
S
Brookes
Charlotte
C
Matheson
Mary
M
Finney
Michelle
M
Kerr
Moyra
M
Hudson
Michael
M
Findlow
Jamie
J
Borrow
Ray
R
Andrews
Nick
N
Kafatos
George
G
Evans
Cariad M
CM
Read
Robert C
RC
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000293:Adolescent; D000328:Adult; D000536:Aluminum Hydroxide / Q000008:administration & dosage; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D003429:Cross Reactions; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006805:Human Experimentation; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008297:Male; D022401:Meningococcal Vaccines / Q000009:adverse effects* / Q000276:immunology*; D051379:Mice; D008875:Middle Aged; D042806:Neisseria lactamica / Q000276:immunology*; D009345:Neisseria meningitidis / Q000276:immunology; D009895:Opsonin Proteins / Q000097:blood / Q000276:immunology; D010919:Placebos / Q000008:administration & dosage; D022142:Secretory Vesicles / Q000276:immunology*; D055815:Young Adult
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D007074:Immunoglobulin G; D022401:Meningococcal Vaccines; D009895:Opsonin Proteins; D010919:Placebos; D000536:Aluminum Hydroxide