Emerging experience with meningococcal serogroup B protein vaccines

Abstract

The successful development of two broadly protective vaccines targeting Neisseria meningitidis serogroup B (MenB); 4CMenB and rLP2086, is the most significant recent advance in meningococcal disease prevention. Areas covered: Here we review the principles underlying the development of each vaccine and the novel methods used to estimate vaccine coverage. We update clinical and post-licensure experience with 4CMenB and rLP2086. Expert commentary: The immunogenicity and acceptable safety profile of 4CMenB and rLP2086 has been demonstrated in clinical trials. Continuing uncertainties exist around the appropriate age groups to be immunized, the degree and duration of efficacy, and the impact on nasopharyngeal carriage which has implications for strategies to interrupt transmission and maximize herd protection effects. Universal vaccination programs such as those undertaken in Quebec and the United Kingdom are providing important information on these issues. The potential for MenB vaccines to prevent infection by other serogroups appears promising, and the impact of MenB vaccines on other pathogenic neisserial species with similar surface proteins warrants further investigation.

Inhibitors of the Neisseria meningitidis PilF ATPase provoke type IV pilus disassembly

“…Because of the rapid evolution of the disease and the severity of the symptoms, industrial and basic research efforts have focused on the design of vaccine strategies (4). Conjugated polysaccharide vaccines have been very successful for specific serogroups, but these approaches also show certain limits due to the diversity and variability of surface structures in N. meningitidis (5,6).…”

Persistence of the immune response after 4CMenB vaccination, and the response to an additional booster dose in infants, children, adolescents, and young adults

“…All MenB IMD strains contain genes for at least one 4CMenB component, and the majority have genes for more than one, although their sequence, surface expression and susceptibility to specific antibody-mediated killing vary widely, potentially providing numerous targets for antibodies induced by vaccination. 41 Vaccine-induced antibodies to any one of the individual vaccine antigens may be sufficient to confer protection against an invasive organism, depending upon the type and amount of antigen the bacterium expresses. This means that subjects vaccinated with 4CMenB are unlikely to need to maintain high levels of antibodies to all four antigens in order to benefit from some degree of protection.…”

Potential benefits of using a multicomponent vaccine for prevention of serogroup B meningococcal disease

“…Immunological data have been comprehensively and extensively reviewed elsewhere (Rappuoli et al, 2018;Toneatto et al, 2017;Watson and Turner, 2016). In summary, robust immune responses to each individual component of 4CMenB have been demonstrated in clinical studies across age groups, including in infants, toddlers, and adolescents.…”

“…In itself, the presence of antigen-encoding genes is not directly predictive of a strain's susceptibility to antibody-mediated killing, since this depends critically upon the bacterial antigen being sufficiently expressed and cross-reactive with the vaccine variant. However, the presence of genes encoding several antigens very likely increases the number of targets for surface-binding by 4CMenB-elicited antibodies (Toneatto et al, 2017).…”