Researchers are one step closer to finding a vaccine that protects against a wide range of serogroup B meningococcal strains that have become the major cause of bacterial meningitis in many regions of Europe and North America, according to new research published Online First in The Lancet Infectious Diseases. A new vaccine for serogroup B Neisseria meningitidis was safe and immunogenic in adolescents, the majority of whom generated bactericidal antibodies that were active against strains that represent 90% of invasive meningococcus serogroup B strains circulating in the USA and Europe.
"Our data suggest that this vaccine is a promising and broadly protective meningococcal serogroup B vaccine candidate…If additional studies show similar immunogenicity and tolerability, this vaccine might help to reduce the global burden of invasive meningococcal disease", explains Peter Richmond from the University of Western Australia School of Paediatrics and Child Health, lead author of the study.
Although strain-specific meningococcal serogroup B vaccines have been developed, for example in Cuba and New Zealand, the development of a broadly protective vaccine against diverse meningococcal serogroup B strains has been challenging. The proteins on the surface of these bacteria, against which an immune response is generated, can vary, making it difficult to develop a vaccine that is effective against many different strains.
The new bivalent recombinant vaccine was developed using two versions (variants) of an antigen, lipoprotein 2086, that is present in at least 98% of all meningococcal serogroup B strains.
This phase 2 trial enrolled 539 healthy adolescents from 25 sites across Australia, Poland, and Spain to test the safety and immunogenicity (the ability to produce an immune response) of the lipoprotein 2086 vaccine. Adolescents are at increased risk of meningococcal infection.
Participants were randomly assigned to three doses (60 µg, 120 µg, or 200 µg of total protein) of vaccine or placebo at 0, 2, and 6 months. Immunogenicity was measured with serum bactericidal assays using human complement (hSBA) to detect protective antibody responses against a panel of eight diverse serogroup B strains.
The results showed that three doses produced an immune response, indicating protection, in 80% to 100% of adolescents.
The vaccine was generally well tolerated in each dosing group. Mild-to-moderate pain at the injection site was the most commonly reported side effect. One vaccine-related serious adverse event occurred after the third 200 µg dose.
The authors conclude: "The high protection indicated by hSBA response to all test strains…suggests that bivalent recombinant lipoprotein 2086 is a broadly protective vaccine and that three doses is sufficient to confer high seroprotection…Future research will define the reactogenicity [the capacity of a vaccine to produce adverse reactions], breadth of coverage, and robustness of immunological protection afforded by the vaccine."
In an accompanying Comment, Muhamed-Kheir Taha and Ala Eddine Deghmane from Institut Pasteur, Paris, France say: "Surveillance of meningococcal isolates and typing should continue and include sequencing of genes that encode factor H binding protein to monitor the emergence or expansion of any escape variants."
Dr Peter Richmond, University of Western Australia School of Paediatrics and Child Health and Telethon Institute for Child Health Research, Subiaco, Australia. T) +61 410 698 280 (mobile) E) peter.richmond@uwa.edu.au
Dr Muhamed-Kheir Taha, Institut Pasteur, Paris, France. T) +33 1 45 68 84 38 E) mktaha@pasteur.fr
Journal
The Lancet Infectious Diseases