In a phase IIB/III study conducted among adolescents in Chile, a multicomponent vaccine — 4CMenB — was immunogenic and safe.

Licensed vaccines are available to protect against meningococcal serogroups A, C, W-135, and Y. Although serogroup B infrequently affects individuals aged >1 year in the U.S., it remains a major cause of meningococcal disease worldwide. Development of a vaccine against this serogroup has been challenging, however, because serogroup B polysaccharide resembles the human neural-cell adhesion molecule and is poorly immunogenic. Investigators have now developed a candidate vaccine, 4CMenB, with four components: three semiconserved surface protein antigens plus a serogroup B outer membrane vesicle preparation.

In a recent manufacturer-sponsored, observer-blind, placebo-controlled, phase IIB/III trial conducted in Chile, investigators examined the immunogenicity and safety of this vaccine. Healthy adolescents aged 11 to 17 years were randomized to receive 4CMenB (1 dose, 2 doses either 1 or 2 months apart, or 3 doses) or three doses of placebo. At 6 months, participants in the one- and two-dose vaccine groups were further randomized to receive a dose of vaccine or placebo, whereas participants in the three-dose vaccine group received placebo, and those in the placebo group received a vaccine dose. Immunogenicity was assessed by analyzing serum bactericidal activity using human complement (hSBA) against three meningococcal reference strains.

Two months after a single dose of vaccine, hSBA titers were waning, although protective levels were maintained in 69% to 81% of vaccinees at 6 months. After two doses, >99% of vaccinees (1040/1044) had titers ≥4. At 6 months, 100% of two-dose recipients had titers considered protective. A third dose of vaccine provided no additional benefit. Local adverse events and systemic reactions were more common after vaccine injections than after placebo injections (e.g., fever in 4% vs. 2%). Two 4CMenB recipients developed juvenile arthritis 170 and 198 days after the third vaccine dose; one of them had experienced joint symptoms before study entry.


Citation(s):

Santolaya ME et al. Immunogenicity and tolerability of a multicomponent meningococcal serogroup B (4CMenB) vaccine in healthy adolescents in Chile: A phase 2b/3 randomised, observer-blind, placebo-controlled study. Lancet 2012 Jan 18; [e-pub ahead of print].

Stephens DS. Prevention of serogroup B meningococcal disease. Lancet 2012 Jan 18; [e-pub ahead of print].