Early clinical experience with a candidate meningococcal B recombinant vaccine (rMenB) in healthy adults

Abstract

Dull (2011) Early clinical experience with a candidate meningococcal B recombinant vaccine (rMenB) in healthy adults, Human Vaccines, 7:7, 781-791, DOI: 10.4161/hv.7.7.15997 To link to this article: https://doi.org/10.4161/hv.7.7.15997 IntroductionVaccination against invasive meningococcal disease is recognized as an optimal measure to prevent disability and mortality; however traditional approaches are not applicable to serogroup B because of the biochemistry of the capsular polysaccharide. 1-4Outer membrane vesicle-based vaccines have successfully limited clonal outbreaks in Cuba, Norway, and New Zealand, but do not provide protection against heterologous strains because they largely rely for their immunogenicity on Porin A, which does not elicit bactericidal antibodies that provide cross protection with non-homologous variants. 2 The need for additional vaccine options against this elusive serogroup resulted in the investigation of surface exposed proteins as vaccine antigens.Several meningococcal surface antigens that are conserved across numerous pathogenic strains were identified using wholegenome sequencing, which subsequently led to the development 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 3-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 mo 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 d 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.

Immune responses to a recombinant, four-component, meningococcal serogroup B vaccine (4CMenB) in adolescents: A phase III, randomized, multicentre, lot-to-lot consistency study

“…Since development, the 4CMenB vaccine has been administered in phase I, and pivotal phase IIb and III studies to over 8000 adults, adolescents and infants and has been shown to be immunogenic, as measured by serum bactericidal assay using human complement (hSBA), to a majority of tested strains within hypervirulent clusters responsible for MenB disease [16][17][18][19][20][21].…”

Persistence of antibodies in adolescents 18−24 months after immunization with one, two, or three doses of 4CMenB meningococcal serogroup B vaccine

“…7 The resulting vaccine contains four protein antigens, 4CMenB (Bexsero ® , Novartis Vaccines, and Diagnostics), which has recently received approval for use from 2 mo of age by the European Medicines Agency (EMA). 8 This vaccine has been shown to be immunogenic and well tolerated when administered in various dose schedules in all age groups from infants to adults, 9,10 including toddlers and our own study in adolescents. We previously demonstrated the immunogenicity and tolerability of the serogroup B meningococcal vaccine, 4CMenB (Bexsero ® ), in 11-17 y-olds randomized to receive 1, 2, or 3 doses at 1, 2, or 6 mo intervals.…”

Defining a protective epitope on factor H binding protein, a key meningococcal virulence factor and vaccine antigen

“…fHbp is a 28 kDa surface-exposed lipoprotein and an important component of two meningococcal vaccines currently in clinical development (6)(7)(8)(9). fHbp plays a prominent role in meningococcal pathogenesis by recruiting human factor H (hfH) to the bacterial surface, thus protecting the bacterium from complement-mediated killing (10)(11)(12).…”