TY - JOUR
T1 - Immunogenicity and tolerability of a multicomponent meningococcal serogroup B (4CMenB) vaccine in healthy adolescents in Chile
T2 - A phase 2b/3 randomised, observer-blind, placebo-controlled study
AU - Santolaya, María Elena
AU - O'Ryan, Miguel L.
AU - Valenzuela, María Teresa
AU - Prado, Valeria
AU - Vergara, Rodrigo
AU - Muñoz, Alma
AU - Toneatto, Daniela
AU - Graña, Gabriela
AU - Wang, Huajun
AU - Clemens, Ralf
AU - Dull, Peter M.
PY - 2012/2
Y1 - 2012/2
N2 - 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.
AB - 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.
KW - Vaccine
KW - meningococcal serogroup B
KW - meningococcal vaccines
KW - Neisseria meningitidis
UR - http://www.scopus.com/inward/record.url?scp=84857238470&partnerID=8YFLogxK
U2 - 10.1016/S0140-6736(11)61713-3
DO - 10.1016/S0140-6736(11)61713-3
M3 - Article
C2 - 22260988
AN - SCOPUS:84857238470
SN - 0140-6736
VL - 379
SP - 617
EP - 624
JO - The Lancet
JF - The Lancet
IS - 9816
ER -