Immunogenicity and safety of investigational vaccine formulations against meningococcal serogroups A, B, C, W, and Y in healthy adolescents

Abstract

This phase 2 study assessed the immunogenicity, safety, and reactogenicity of investigational formulations of meningococcal ABCWY vaccines, consisting of recombinant proteins (rMenB) and outer membrane vesicle (OMV) components of a licensed serogroup B vaccine, combined with components of a licensed quadrivalent meningococcal glycoconjugate vaccine (MenACWY-CRM). A total of 495 healthy adolescents were randomized to 6 groups to receive 2 doses (Months 0, 2) of one of 4 formulations of rMenB antigens, with or without OMV, combined with MenACWY-CRM, or 2 doses of rMenB alone or one dose of MenACWY-CRM then a placebo. Immunogenicity was assessed by serum bactericidal assay with human complement (hSBA) against serogroups ACWY and serogroup B test strains; solicited reactions and any adverse events (AEs) were assessed. Two MenABCWY vaccinations elicited robust ACWY immune responses, with higher seroresponse rates than one dose of MenACWY-CRM. Bactericidal antibody responses against the rMenB antigens and OMV components were highest in subjects who received 2 doses of OMV-containing MenABCWY formulations, with 68% of subjects achieving hSBA titers 5 against each of the serogroup B test strains. After the first dose, solicited local reaction rates were higher in the MenABCWY or rMenB groups than the MenACWY-CRM group, but similar across groups after the second dose, consisting mainly of transient injection site pain. Fever ( 38.0 C) was rare and there were no vaccine-related serious AEs. In conclusion, investigational MenABCWY formulations containing OMV components elicited highly immunogenic responses against meningococcal serogroups ACWY, as well as serogroup B test strains, with an acceptable safety profile. [NCT01210885]

Four-year antibody persistence and response to a booster dose of a pentavalent MenABCWY vaccine administered to healthy adolescents and young adults

“…Out of the 485 eligible participants who completed the primary study, 28 79 participants were enrolled in this second extension, with 33 participants who previously received 2 doses of MenABCWY+OMV (Group III), and 46 participants who received 1 dose of MenACWY-CRM (Group VI). This extension also included 50 newly-recruited non-vaccinated participants (Group VII).…”

“…A phase 2 randomized controlled study conducted in Panama, Colombia, and Chile evaluated safety and immunogenicity of 4 different MenABCWY vaccine candidates in healthy adolescents. 28 The candidate vaccine that was selected for further investigation is composed of MenACWY conjugated to a carrier protein cross reactive material 197 (CRM 197 ) combined with recombinant proteins from serogroup B and outer membrane vesicle from New Zealand strain NZ98/254 (MenABCWY+OMV). In the primary study, 28 2 doses of the investigational MenABCWY+OMV vaccine given 2 months apart induced substantial immune responses against all serogroups and the candidate vaccine was well-tolerated.…”

“… 28 The candidate vaccine that was selected for further investigation is composed of MenACWY conjugated to a carrier protein cross reactive material 197 (CRM 197 ) combined with recombinant proteins from serogroup B and outer membrane vesicle from New Zealand strain NZ98/254 (MenABCWY+OMV). In the primary study, 28 2 doses of the investigational MenABCWY+OMV vaccine given 2 months apart induced substantial immune responses against all serogroups and the candidate vaccine was well-tolerated. 28 In a first follow-up extension study, 29 the immune responses against serogroups A, C, W and Y persisted for up to 12 months.…”

“…In the primary study, 28 2 doses of the investigational MenABCWY+OMV vaccine given 2 months apart induced substantial immune responses against all serogroups and the candidate vaccine was well-tolerated. 28 In a first follow-up extension study, 29 the immune responses against serogroups A, C, W and Y persisted for up to 12 months. However, levels of antibodies against serogroup B test strains waned by 6 months after vaccination and then stabilized up to 12 months.…”

Protecting the most vulnerable age group: a review of MenACWY-TT immunogenicity and safety in infants

“…Currently, there are two MenB vaccines available: MenB-FHbp (Trumenba®; Pfizer Inc, Philadelphia, PA, USA) [65] and 4CMenB (Bexsero®; GSK Vaccines, Srl, Siena, Italy) [66]. Additionally, two different formulations of pentavalent vaccines targeting serogroups A, B, C, W, and Y are currently under evaluation, and available data have indicated promising results [67][68][69][70]. Another pentavalent vaccine containing capsular polysaccharides from serogroups A, C, W, X, and Y, intended to combat increased rates of MenX disease in Africa, has also been shown to be immunogenic in phase 1 evaluations [71].…”