The Lancet  
Feb 18, 2012  Volume 379  Number 9816  p589 – 684 e33
http://www.thelancet.com/journals/lancet/issue/current

Comment
Prevention of serogroup B meningococcal disease
David S Stephens
Preview
In The Lancet, María Elena Santolaya and colleagues1 describe the immunogenicity and safety in healthy Hispanic adolescents of a new multicomponent vaccine, 4CMenB, a potential breakthrough in protection against meningitis, sepsis, and other infections caused by Neisseria meningitidis serogroup B. With the successful development and use of effective polysaccharide-protein glycoconjugate vaccines for serogroups A, C, Y, and W-135,2,3 serogroup B N meningitidis (distinguished by the expression of an [α2→8]-linked polysialic acid capsule) is now the leading cause of meningococcal disease, especially in infants and young children in many countries.

Articles
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
María Elena Santolaya, Miguel L O’Ryan, María Teresa Valenzuela, Valeria Prado, Rodrigo Vergara, Alma Muñoz, Daniela Toneatto, Gabriela Graña, Huajun Wang, Ralf Clemens, Peter M Dull, for the V72P10 Meningococcal B Adolescent Vaccine Study group

Summary
Background
Effective glycoconjugate vaccines against Neisseria meningitidis serogroups A, C, W-135, and Y have been developed, but serogroup B remains a major cause of severe invasive disease in infants and adolescents worldwide. We assessed immunogenicity and tolerability of a four-component vaccine (4CMenB) in adolescents.

Methods
We did a randomised, observer-blind, placebo-controlled, study at 12 sites in Santiago and Valparaíso, Chile. Adolescents aged 11—17 years received one, two, or three doses of 4CMenB at 1 month, 2 month, or 6 month intervals. Immunogenicity was assessed as serum bactericidal activity using human complement (hSBA) against three reference strains for individual vaccine antigens, and assessed by ELISA against the fourth strain. Local and systemic reactions were recorded 7 days after each vaccination, and adverse events were monitored throughout the study. Participants were initially randomised to five groups (3:3:3:3:1) during the primary phase to receive either one dose, two doses 1 or 2 months apart, or three doses of 4CMenB, or three doses of placebo, with an additional three groups generated for the booster phase. All subjects received at least one dose of 4CMenB. Geometric mean titres, proportions of participants with serum bactericidal antibody titres of 4 or more, and Clopper-Pearson 95% CIs were calculated. The study is registered with ClinicalTrials.gov, number NCT00661713.

Findings
Overall, 1631 adolescents (mean age 13·8 [SD 1·9] years) received at least one dose of 4CMenB. After two or three doses, 99—100% of recipients had hSBA titres of 4 or more against test strains, compared with 92—97% after one dose (p<0·0145) and 29—50% after placebo. At 6 months 91—100% of participants still had titres of 4 or more for each strain after two or three doses, but only 73—76% after one dose; seroresponse rates reached 99—100% for each strain after second or third doses at 6 months. Local and systemic reaction rates were similar after each 4CMenB injection and did not increase with subsequent doses, but remained higher than placebo. No vaccine-related serious adverse events were reported and no significant safety signals were identified.

Interpretation
On the basis of immunogenicity responses this study provides evidence for an adolescent 4CMenB vaccine schedule of two doses, 1—6 months apart, to provide protection against meningococcal B infection. The extent of this protection against meningococcus B variants circulating worldwide will be determined by national surveys.

Funding
Novartis Vaccines and Diagnostics.