Breadth of coverage against a panel of 110 invasive disease isolates, immunogenicity and safety for 2 and 3 doses of an investigational MenABCWY vaccine in US adolescents - Results from a randomized, controlled, observer-blind phase II study.
Vaccine
; 36(35): 5309-5317, 2018 08 23.
Article
in En
| MEDLINE
| ID: mdl-30061029
ABSTRACT
BACKGROUND:
Neisseria meningitidis serogroups A, B, C, W and Y cause most meningococcal disease worldwide. An investigational MenABCWY vaccine combining serogroup B antigens and a meningococcal ACWY CRM197-glycoconjugate vaccine (MenACWY-CRM) could provide protection against all 5 serogroups. Complement mediated bactericidal activity induced by MenABCWY was tested against a panel of 110 randomly-selected serogroup B strains causing invasive disease in the US to evaluate the vaccine's breadth of coverage (BoC).METHODS:
We conducted this observer-blind study (NCT02140762) and its extension (NCT02285777) in 8 centers in the US. Adolescents aged 10-18â¯years were randomized (11) to receive either 3 MenABCWY doses (MenABCWY group), on a 0, 2, 6-month (M) schedule or a single MenACWY-CRM dose at M2 and placebo at 0,6-M (Control group). MenABCWY BoC was calculated as (1â¯-â¯relative risk)â¯×â¯100 (relative riskâ¯=â¯ratio between the percentage of samples seronegative at 14 dilution against the selected strains in the MenABCWY vs Control group). BoC was determined at 1â¯M and 4â¯M after 2 and 3 doses, using an endogenous complement serum bactericidal assay. Immunogenicity and safety were assessed.RESULTS:
301 and 189 adolescents were vaccinated in the parent and extension study, respectively. At 1â¯M post-vaccination, the BoC of MenABCWY across the 110 serogroup B strains was 67% (95%CI 65-69) after 2 doses and 71% (95%CI 69-73) after 3 doses. BoC decreased to 44% (95%CI 41-47) and 51% (95%CI 48-55) at 4â¯M after 2 and 3 MenABCWY doses, respectively. Robust immune responses to antigen-specific test strains for each serogroup were observed at all timepoints in the MenABCWY group. No reactogenicity or safety concerns arose during the study.CONCLUSION:
Two or 3 doses of MenABCWY showed similar BoC against the panel of invasive US serogroup B isolates and comparable immunogenicity against the antigen-specific test strains, with no safety concerns identified.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Meningococcal Vaccines
/
Meningococcal Infections
Type of study:
Clinical_trials
/
Etiology_studies
Limits:
Adolescent
/
Child
/
Female
/
Humans
/
Male
Language:
En
Journal:
Vaccine
Year:
2018
Document type:
Article
Publication country:
HOLANDA
/
HOLLAND
/
NETHERLANDS
/
NL
/
PAISES BAJOS
/
THE NETHERLANDS