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
| Autor: | Jo Anne Welsch, Shelly Senders, Bikash Verma, Daniela Toneatto, Thomas Klein, Silvia Barbi, Igor Smolenov, Paola Pedotti, Brandon Essink |
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| Rok vydání: | 2018 |
| Předmět: |
Male
Adolescent Phases of clinical research Meningococcal Vaccines Meningococcal vaccine Neisseria meningitidis Placebo Meningococcal disease medicine.disease_cause Serogroup 03 medical and health sciences 0302 clinical medicine Antigen 030225 pediatrics Medicine Humans 030212 general & internal medicine Vaccines Combined Child Reactogenicity Vaccines Conjugate General Veterinary General Immunology and Microbiology business.industry Immunogenicity Public Health Environmental and Occupational Health medicine.disease Meningococcal Infections Infectious Diseases Immunology Molecular Medicine Female business |
| Zdroj: | Vaccine. 36(35) |
| ISSN: | 1873-2518 |
| Popis: | 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 CRM 197 -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 10–18 years were randomized (1:1) 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 (1 − relative risk) × 100 (relative risk = ratio between the percentage of samples seronegative at 1:4 dilution against the selected strains in the MenABCWY vs Control group). BoC was determined at 1 M and 4 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 1 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 4 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. |
| Databáze: | OpenAIRE |
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