Safety and immunogenicity of a meningococcal B bivalent rLP2086 vaccine in healthy toddlers aged 18-36 months: a phase 1 randomized-controlled clinical trial.
BACKGROUND
A bivalent, recombinant, factor H-binding protein (rLP2086) vaccine was developed to protect against invasive Neisseria meningitidis serogroup B (MnB) in children and adolescents.


METHODS
Healthy toddlers (N = 99) were enrolled to 3 ascending dose-level cohorts (20, 60 or 200 μg). Within each cohort (n = 33), subjects were randomized to receive an initial formulation of the bivalent rLP2086 vaccine at 0, 1 and 6 months or hepatitis A vaccine/placebo control (2:1 ratio). Reactogenicity was assessed by parental reporting of local and systemic reactions using electronic diaries and reports of unsolicited adverse events. Immunogenicity was assessed by serum bactericidal activity assay using human complement and rLP2086-specific IgG binding.


RESULTS
The vaccine was considered to be well tolerated. Tenderness was the most frequently reported local reaction. Upper respiratory tract infection was the most commonly reported adverse event and occurred more frequently in the control group. Three cases (200 μg dose) of severe erythema that did not interfere with limb movement were reported. Four toddlers developed fever >40.0°C, 3 in the 200 μg group and 1 in the 60 μg group. Postdose 3, seroconversion (serum bactericidal activity assay using human complement ≥4-fold rise from baseline) was observed in 61.1-88.9% of participants against MnB strains expressing LP2086 variants homologous or nearly homologous to vaccine antigens and 11.1-44.4% against MnB strains expressing heterologous LP2086 variants. Seroconversion was observed in 77.8-100% of participants against additional, exploratory MnB strains expressing vaccine-homologous or heterologous LP2086 variants.


CONCLUSIONS
This study shows that the bivalent rLP2086 vaccine is well tolerated and immunogenic in toddlers.
Vaccinology and Immunology Research Trials Unit, Women's and Children's Hospital and School of Paediatrics and Reproductive Health, University of Adelaide, North Adelaide, South Australia. helen.marshall@adelaide.edu.au
Helen S
HS
Marshall
Peter C
PC
Richmond
Michael D
MD
Nissen
Qin
Q
Jiang
Annaliesa S
AS
Anderson
Kathrin U
KU
Jansen
Graham
G
Reynolds
John B
JB
Ziegler
Shannon L
SL
Harris
Thomas R
TR
Jones
John L
JL
Perez
D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D001770:Blood Bactericidal Activity; D002675:Child, Preschool; D003165:Complement System Proteins / Q000276:immunology; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D008297:Male; D008589:Meningococcal Infections / Q000517:prevention & control; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D038541:Neisseria meningitidis, Serogroup B / Q000276:immunology*; D010919:Placebos / Q000008:administration & dosage; D014611:Vaccination / Q000379:methods; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D007074:Immunoglobulin G; D022401:Meningococcal Vaccines; D010919:Placebos; D014614:Vaccines, Synthetic; C484699:factor H-binding protein, Neisseria meningitidis; D003165:Complement System Proteins