Immunogenicity and Reactogenicity of a Reduced Schedule of a 4-component Capsular Group B Meningococcal Vaccine: A Randomized Controlled Trial in Infants

Abstract

Background: The 4-component capsular group B meningococcal vaccine (4CMenB) was licensed as a 4-dose infant schedule but introduced into the United Kingdom as 3 doses at 2, 4, and 12 months of age. We describe the immunogenicity and reactogenicity of the 2 + 1 schedule in infants.

Methods: Infants were randomized to receive 4CMenB with routine immunizations (test group) at 2, 4, and 12 months or 4CMenB alone at 6, 8, and 13 months of age (control group). Serum bactericidal antibody (SBA) assay against a serogroup B meningococcal reference strain (44/76-SL), memory B-cell responses to factor H binding protein, Neisseria adhesion protein A, Neisseria heparin binding antigen, Porin A (PorA), and reactogenicity was measured.

Results: One hundred eighty-seven infants were randomized (test group: 94; control group: 93). In the test group, 4CMenB induced SBA titers above the putative protective threshold (1:4) after primary and booster doses in 97% of participants. Postbooster, the SBA GMT (72.1; 95% confidence interval [CI], 51.7-100.4) was numerically higher than the serum bactericidal antibody geometric mean titre (SBA GMT) determined post-primary vaccination (48.6; 95% CI, 37.2-63.4). After primary immunizations, memory B-cell responses did not change when compared with baseline controls, but frequencies significantly increased after booster. Higher frequency of local and systemic adverse reactions was associated with 4CMenB.

Conclusions: A reduced schedule of 4CMenB was immunogenic and established immunological memory after booster.

Keywords: 4-component capsular group B meningococcal vaccine; 4CMenB; immunogenicity; memory B cells; meningococcal disease; reactogenicity; reduced schedule.

Figure 1.

Clinical trial flow diagram (CONSORT diagram). Children were considered not eligible for the study if they failed to fulfill all inclusion criteria (healthy infants of 2 Caucasian parents, born between 37 and 42 weeks of gestation and aged 8–12 weeks at the time of first visit; parent or legal guardian willing and able to comply with the requirements of the protocol, who had Internet access for the duration of the study; parent/legal guardian who had given informed consent for their child’s participation in the study) or if they had any exclusion criteria (infants with a history of invasive MenB disease, previous vaccination with an MenB vaccine, a household contact with a case of confirmed bacterial meningitis, confirmed or suspected immunodeficiency, family history of congenital or hereditary immunodeficiency or maternal HIV, in receipt of >1 week of immunosuppressants or immune-modifying drugs, a history of allergy to a component of the vaccine, major congenital defects or serious chronic illness, history of neurologic disorders, or administration of immunoglobulins or any blood products since birth). Abbreviation: SBA, serum bactericidal antibody. *One control group participant received routine and 4CMenB vaccines at the 12-month visit (V10) rather than at the 13-month visit (V12).

Figure 2.

Proportion of individuals with human complement serum bactericidal antibody titers ≥4 after postprimary, prebooster, and postbooster immunizations in the test group. Abbreviation: SBA, serum bactericidal antibody.

Figure 3.

Dot plots of antigen-specific memory B-cells after ELISpot assay for the test group and control group at different time points (mean and 95% confidence interval). Test group: Postprimary^T: 1 month after primary immunizations – 5 months of age; Prebooster^T: 8 months after primary immunizations – 12 months of age; Postbooster: 1 month after booster immunizations – 13 months of age. Control group: Baseline^C: 6 months of age; Postprimary^C: 4 months after primary immunizations – 12 months of age; Prebooster^C: 5 months after primary immunizations – 13 months of age. Abbreviations: NHBA, Neisseria heparin binding antigen; PBMC, peripheral blood mononuclear cell.