Broad-spectrum meningitis vaccine shows promise in phase II
MedWire News: A new vaccine could prevent the vast majority of meningitis cases, results of an international randomized placebo-controlled phase II trial indicate.
When tested in more than 500 healthy adolescents, the bivalent recombinant factor H- binding protein (recombinant lipoprotein 2086) vaccine was immunogenic, induced robust activity against diverse strains of meningococcal serogroup B, and was well tolerated.
"Our data suggest that this vaccine is a promising and broadly protective meningococcal serogroup B vaccine candidate," write Peter Richmond (Princess Margaret Hospital for Children, Subiaco, Australia) and co-authors in The Lancet Infectious Diseases.
They add: "Future and ongoing clinical trials will define the reactogenicity, breadth of coverage, and robustness of immunological protection afforded by the vaccine."
The vaccine was designed to protect against Neisseria meningitidis serogroup B, which is the predominant cause of invasive meningococcal disease. Currently available vaccines protect against other serogroups, but there is a "major unmet need" for a broadly protective vaccine, says the team.
Richmond and colleagues enrolled 539 healthy adolescents from 25 sites in Australia, Poland, and Spain. They were randomly assigned to receive ascending doses of vaccine (60, 120, or 200 µg) or placebo at 0, 2, and 6 months.
Immunogenicity was measured by serum bactericidal assays using human complement (hSBA) against eight diverse meningococcus serogroup B strains. The coprimary endpoints were seroconversion for the two indicator strains (PMB1745 and PMB17).
Results showed that the proportion of participants responding to the vaccine was similar for the two largest doses and ranged from 75.6% to 100.0% for the 120 µg dose and from 67.9% to 99.0% for the 200 µg dose.
The frequencies of seroconversion for the PMB1745 reference strain were 89.5%, 92.8%, 94.0%, and 5.5% in the 60 µg, 120 µg, 200 µg, and placebo groups, respectively. For the PMB17 reference strain, seroconversion rates were 81.0%, 86.6%, 84.8%, and 1.3%, respectively.
"Vaccination with recombinant lipoprotein 2086 resulted in robust hSBA titres against each of the eight meningococcus serogroup B test strains," note Richmond et al.
The vaccine had an "acceptable" safety profile, say the researchers. Overall, adverse events were reported by 81.8%, 38.9%, 47.2%, and 44.6% of participants in the 60 µg, 120 µg, 200 µg, and placebo groups, respectively.
The most common local reaction was mild-to-moderate injection site pain, while systemic events, including fatigue and headache, were generally mild to moderate. Fevers were rare and generally mild, and did not increase in incidence or severity with repeated dosing.
There was also one anaphylactic reaction, which the researchers say warrants further investigation in view of the potential for hypersensitivity to lipoprotein 2086.
"The choice of the strains for future serum bactericidal assays should also account for global and local epidemiological distributions of the alleles that encode factor H- binding protein," the researchers conclude.
"These data would be crucial for future recommendations for the use of the vaccine because genetically diverse isolates might circulate in different regions."
By Joanna Lyford