An investigational recombinant vaccine against meningococcal serogroup B was immunogenic when given along with other vaccines in a study of more than 1,800 healthy infants.
The vaccine "was immunogenic, generally well tolerated, and showed minimal interference with routine vaccines in the first year of life. The flexibility in schedule allows it to be incorporated into a range of country-specific immunization schedules and for primary immunization to be completed in early infancy," said Dr. Nicoletta Gossger of Oxford Vaccine Group, University of Oxford, England, and her associates (JAMA 2012;307:573-82).
Currently available capsular polysaccharide-based vaccines protect against Neisseria meningitidis serogroups C, W-135, and Y but not B, because its capsular polysaccharide is poorly immunogenic in humans. Novartis Vaccines and Diagnostics developed a multicomponent serogroup B meningococcal vaccine (4CMenB) by combining novel antigens with outer membrane vesicles (OMV). Small studies in infants demonstrated immunogenicity of 4CMenB against reference strains (Clin. Infect. Dis. 2010;51:1127-37; Pediatr. Infect. Dis J. 2010;29:e71-9).
In the current phase IIb, open-label, parallel group, randomized controlled trial funded by the company, Dr. Gossger and her associates assessed the immunogenicity and reactogenicity of 4CMenB in 1,885 healthy, full-term 2-month-old infants from 60 centers in six European countries. The infants were randomized to one of three primary 4CMenB schedules: ages 2, 4, and 6 months, together with routine infant vaccines (concomitant); 2, 4, and 6 months, with routine vaccines given separately at 3, 5, and 7 months (intercalated); and 2, 3, and 4 months, concomitantly with routine infant vaccines (accelerated).
A control group received the diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliomyelitis and Haemophilus influenzae type b conjugate vaccine (Infanrix hexa) and the 7-valent pneumococcal conjugate vaccine (Prevnar) only at 2, 3, and 4 months. All immunization time points used in the study were chosen to reflect schedules currently used in different countries, Dr. Gossger and her associates noted.
Median age of the infants at enrollment was 68.7 days for all groups, 48%-53% of each group was boys, and 93% of all participants were white. Human complement serum bactericidal activity (hSBA) was assessed against three MenB strains specific for vaccine antigens. After immunization with 4CMenB and routine vaccines together at either 2, 4, and 6 months or 2, 3, and 4 months, 99% or more of participants had hSBA titers of 1:5 or greater (considered protective) for two of the strains (44/76-SL and 5/99) in the modified intention-to-treat immunogenicity analysis, which included 1,636 of the entire cohort.
For strain NZ98/254, which was chosen to determine the immunogenicity of the OMV, the percentages were 79% following the concomitant schedule, 86% for the intercalated schedule, and 82% following the accelerated schedule. Immune responses to all three strains met the predefined sufficiency criteria, the investigators reported.
Responses to routine vaccines given with 4CMenB were noninferior to routine vaccines alone for all antigens, except for the responses to pertactin and serotype 6B pneumococcal polysaccharide. This is "unlikely to be of clinical significance," based on experience with other vaccines, Dr. Gossger and her associates commented.
During the study, less than 1% of the infants had severe erythema, swelling, or induration at the vaccination sites. Nonetheless, 12% to 16% in the concomitant and accelerated groups, respectively, had severe local pain after a dose of 4CMenB, compared with 1% to 3% after doses of DTaP-HBV-IPV/Hib or PCV7 in the control group.
Fever after any vaccination was reported in 80% the concomitant group and 76% in the accelerated group, compared with 51% in the control group and 71% in the intercalated group. For the intercalated group, there were twice as many immunization days, and thus there was more opportunity for fever to occur, they noted.
There were 166 serious adverse events reported in 158 infants, 63 (10%) in the concomitant group, 57 (9%) in the intercalated group, 19 (6%) in the accelerated group, and 19 (6%) in the control group. Of these adverse events, 20 (9 concomitant, 7 intercalated, 3 accelerated, and 1 control) were considered to be possibly related to 4CMenB or routine vaccinations.
"If licensed, the decisions regarding vaccine introduction will require detailed assessment of potential vaccine coverage at a regional level and monitoring after implementation to determine the accuracy of such predictions. Nevertheless, this vaccine could potentially provide improved protection for infants against meningococcal disease beyond the protection provided by currently licensed vaccines," Dr. Gossger and her associates said.
This study was funded by Novartis Vaccines and Diagnostics. Dr. Gossger reported no relevant financial disclosures. Several of the other study authors reported financial relationships with Novartis and other vaccine manufacturers and noncommercial funding bodies.