BACKGROUND: The development of a broadly protective vaccine against meningococcal serogroup B is a well-recognized public health need. Whole-genome sequencing was used to identify meningococcal surface proteins that are conserved across strains. These proteins were incorporated into two investigational vaccines. METHODS: Three randomized studies were performed to evaluate a three-component recombinant meningococcal serogroup B vaccine (rMenB) and rMenB plus outer membrane vesicles from the Norwegian outbreak strain 44/76 (rMenB+OMVNW). Participants were randomized to receive 3 or 4 doses of rMenB or rMenB+OMVNW or control vaccines and provided sera for exploratory immunogenicity testing against a panel of meningococcal serogroup B strains. A booster dose was administered 12 months after the initial primary series in one of the studies. The control cohort received a licensed quadrivalent meningococcal polysaccharide vaccine against serogroups A, C, W-135 and Y as well as hepatitis B vaccine as safety comparators. Solicited reactions within 7 days of any vaccination and adverse events throughout the studies were recorded. RESULTS:One hundred four participants enrolled into the clinical trials. Both rMenB and rMenB+OMVNW induced immune responses to multiple serogroup B strains in the majority of participants. Compared with rMenB, rMenB+OMVNW appeared somewhat more immunogenic and reactogenic; the study was not adequately powered for statistical assessment of these small differences. Both investigational vaccines were more reactogenic than the licensed vaccines. Few vaccinees discontinued any study due to reactogenicity to any study vaccine administered. CONCLUSION: Based on the immunogenicity and reactogenicity results in these participants, both rMenB and rMenB+OMVNW were promising candidates for further investigation.
RCT Entities:
BACKGROUND: The development of a broadly protective vaccine against meningococcal serogroup B is a well-recognized public health need. Whole-genome sequencing was used to identify meningococcal surface proteins that are conserved across strains. These proteins were incorporated into two investigational vaccines. METHODS: Three randomized studies were performed to evaluate a three-component recombinant meningococcal serogroup B vaccine (rMenB) and rMenB plus outer membrane vesicles from the Norwegian outbreak strain 44/76 (rMenB+OMVNW). Participants were randomized to receive 3 or 4 doses of rMenB or rMenB+OMVNW or control vaccines and provided sera for exploratory immunogenicity testing against a panel of meningococcal serogroup B strains. A booster dose was administered 12 months after the initial primary series in one of the studies. The control cohort received a licensed quadrivalent meningococcal polysaccharide vaccine against serogroups A, C, W-135 and Y as well as hepatitis B vaccine as safety comparators. Solicited reactions within 7 days of any vaccination and adverse events throughout the studies were recorded. RESULTS: One hundred four participants enrolled into the clinical trials. Both rMenB and rMenB+OMVNW induced immune responses to multiple serogroup B strains in the majority of participants. Compared with rMenB, rMenB+OMVNW appeared somewhat more immunogenic and reactogenic; the study was not adequately powered for statistical assessment of these small differences. Both investigational vaccines were more reactogenic than the licensed vaccines. Few vaccinees discontinued any study due to reactogenicity to any study vaccine administered. CONCLUSION: Based on the immunogenicity and reactogenicity results in these participants, both rMenB and rMenB+OMVNW were promising candidates for further investigation.
Authors: Enrico Malito; Agnese Faleri; Paola Lo Surdo; Daniele Veggi; Giulietta Maruggi; Eva Grassi; Elena Cartocci; Isabella Bertoldi; Alessia Genovese; Laura Santini; Giacomo Romagnoli; Erica Borgogni; Sébastien Brier; Carla Lo Passo; Maria Domina; Flora Castellino; Franco Felici; Stijn van der Veen; Steven Johnson; Susan M Lea; Christoph M Tang; Mariagrazia Pizza; Silvana Savino; Nathalie Norais; Rino Rappuoli; Matthew J Bottomley; Vega Masignani Journal: Proc Natl Acad Sci U S A Date: 2013-02-08 Impact factor: 11.205
Authors: Puiying A Mak; George F Santos; Kelly-Anne Masterman; Jeff Janes; Bill Wacknov; Kay Vienken; Marzia Giuliani; Ann E Herman; Michael Cooke; M Lamine Mbow; John Donnelly Journal: Clin Vaccine Immunol Date: 2011-06-29
Authors: Maria Elena Santolaya; Miguel O'Ryan; María Teresa Valenzuela; Valeria Prado; Rodrigo F Vergara; Alma Muñoz; Daniela Toneatto; Gabriela Graña; Huajun Wang; Peter M Dull Journal: Hum Vaccin Immunother Date: 2013-06-28 Impact factor: 3.452
Authors: R Gasparini; D Panatto; N L Bragazzi; P L Lai; A Bechini; M Levi; P Durando; D Amicizia Journal: J Immunol Res Date: 2015-08-17 Impact factor: 4.818
Authors: Andrew J Ullmann; Martin Schmidt-Hieber; Hartmut Bertz; Werner J Heinz; Michael Kiehl; William Krüger; Sabine Mousset; Stefan Neuburger; Silke Neumann; Olaf Penack; Gerda Silling; Jörg Janne Vehreschild; Hermann Einsele; Georg Maschmeyer Journal: Ann Hematol Date: 2016-06-24 Impact factor: 3.673