Bactericidal activity of sera from adolescents vaccinated with bivalent rLP2086 against meningococcal serogroup B outbreak strains from France

• Published in: Vaccine Vol. 35; no. 11; pp. 1530 - 1537
• Main Authors: Taha, Muhamed-Kheir, Hawkins, Julio Cesar, Liberator, Paul, Deghmane, Ala-Eddine, Andrew, Lubomira, Hao, Li, Jones, Thomas R., McNeil, Lisa K., O’Neill, Robert E., Perez, John L., Jansen, Kathrin U., Anderson, Annaliesa S.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 13.03.2017; Elsevier Limited; Elsevier
• Subjects: Adolescent; adolescents; Age; Allergy and Immunology; antibacterial properties; Antigens; Antigens, Bacterial; Antigens, Bacterial - analysis; Antigens, Bacterial - genetics; Antigens, Bacterial - immunology; Bacteria; Bacterial Proteins; Bacterial Proteins - analysis; Bacterial Proteins - genetics; Bacterial Proteins - immunology; binding proteins; Bivalent rLP2086; Blood Bactericidal Activity; blood serum; Child; complement; Complement System Proteins; Complement System Proteins - immunology; Data analysis; Disease Outbreaks; Epidemics; Factor H binding protein; Female; Females; fluorescence; France; France - epidemiology; Funding; Gene Expression Profiling; Human health and pathology; Humans; Immune response; Immunology; Infectious diseases; Invasive meningococcal disease; Life Sciences; Male; MenB-FHbp; Meningitis; Meningococcal Vaccines; Meningococcal Vaccines - administration & dosage; Meningococcal Vaccines - immunology; Microbial Viability; Neisseria meningitidis; Neisseria meningitidis serogroup B; Neisseria meningitidis, Serogroup B - genetics; Neisseria meningitidis, Serogroup B - immunology; Neisseria meningitidis, Serogroup B - isolation & purification; Outbreak; Outbreaks; Proteins; risk; Sepsis; sequence analysis; serotypes; United States; vaccination; Vaccines; Vaccinology; France; Europe; ANE, France; USA; United States; Factor H binding protein; Invasive meningococcal disease; Bivalent rLP2086; Outbreak; MenB-FHbp; Neisseria meningitidis serogroup B
• ISSN: 0264-410X; 1873-2518; 1873-2518; 0264-410X
• DOI: 10.1016/j.vaccine.2017.01.066

•French MnB outbreak strains were characterized by WGS and FHbp surface expression.•Bactericidal activity of sera from bivalent rLP2086 vaccinees was evaluated.•MnB outbreak strains expressed vaccine-heterologous FHbp variants.•Response rates after vaccine dose 3 were ⩾73% against all strains (range, 73–100%).•Bivalent rLP2086 vaccination elicits broad protection against MnB outbreak strains. Bivalent rLP2086 (Trumenba®; MenB-FHbp), composed of two factor H binding proteins (FHbps), is a vaccine approved in the United States for prevention of Neisseria meningitidis serogroup B (MnB) invasive meningococcal disease (IMD). Bactericidal activity of sera from subjects vaccinated with bivalent rLP2086 was assessed against MnB isolates from recent disease outbreaks in France. MnB isolates from IMD cases were characterized by whole genome sequencing and FHbp expression was assessed using a flow cytometry-based assay. Sera from subjects (11–<19years old) vaccinated with bivalent rLP2086 at 0, 2, and 6months were evaluated. Bactericidal activity was measured in serum bactericidal assays using human complement (hSBAs). The response rate (RR) represents the percentage of subjects with an hSBA titer ⩾1:4. The six MnB outbreak isolates expressed diverse FHbp variants: A22, B03, B24 (two isolates), B44, and B228. FHbp expression levels ranged from 1309 to 8305 (mean fluorescence intensity units). The RR of preimmune sera from subjects was 7% to 27%. RRs increased for all isolates after each vaccine dose. After two doses, RRs ranged from 40% to 93%. After dose 3, RRs were ⩾73% for all isolates (range, 73%–100%). Each of the representative French outbreak isolates was killed by sera from subjects vaccinated with bivalent rLP2086. Vaccination elicited an immune response with bactericidal activity against these diverse isolates in a large proportion of subjects at risk. These results provide additional support for the licensure strategy of testing MnB strains expressing vaccine-heterologous FHbp variants in hSBAs and further illustrate the breadth of efficacy of this protein-based MnB vaccine.