Effectiveness of a Serogroup B and C Meningococcal Vaccine Developed in Cuba

Abstract

INTRODUCTION Serogroup B meningococcal outer membrane vesicle vaccines have been effective against vaccine-type strains, but their effectiveness against heterologous strains has been controversial. The Cuban VA-MENGOC-BC vaccine is of this type, but also includes meningococcus C capsular polysaccharide.OBJECTIVES Assess the effectiveness of VA-MENGOC-BC in reducing meningococcal disease caused by homologous or heterologous serogroup B strains and its serological effectiveness against meningococcus C. METHODS A review of studies of VA-MENGOC-BC's application in Cuba, Brazil, Uruguay and Colombia was carried out to examine the vaccine's effectiveness in reducing meningococcal disease during serogroup B outbreaks. Serological effectiveness against serogroup C determined in these studies (indicated by bactericidal antibody titers before and after vaccination) was also analyzed.RESULTS VA-MENGOC-BC's effectiveness against homologous serogroup B strains has consistently been greater than 80% in all age groups. Effectiveness in heterologous contexts was also above 80% in individuals aged >4 years. Lower effectiveness in heterologous contexts was found in Brazilian children aged <2 years, although still >50%. Effectiveness increased when assessed based on mortality rates, as well as in cases of clinically severe meningococcal disease. The carrier-state pattern was modifi ed after vaccination with reduction of hypervirulent lineages. Some 60% of infants (aged <1 year) attained protective bactericidal antibody titers against serogroup C. Higher protection rates were achieved in older children. CONCLUSIONSIn addition to prevention of meningococcal disease caused by homologous serogroup B strains, VA-MENGOC-BC should be considered for heterologous contexts. It is protective against serogroup C in all age groups.

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“…This is a bivalent meningococcal vaccine based on OMVs from group B and group C capsular polysaccharide. It has been successfully used in Cuba and other countries since 1989 to control epidemic meningococcal disease, with an excellent safety profile [29] , [30] .…”

“…Neisseria meningitidis OMVs have also been used as adjuvant -named AFPL1- in several vaccine candidates. This adjuvant is a complex nano-structure containing native lipopolysaccharide (LPS), PorB, and other MAMPs recognized by TLR-4, TLR-2 and TLR-9 receptors on APCs [14] , [29] . OMVs stimulate the production of IFNγ, IL-2, IL-12, pro-inflammatory cytokines (TNFα, IL-1β, IL-8) and chemokines (MIP1-α, MIP1-β).…”

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“…N. meningitidis OMVs, at 50 μg per dose, are a component of antimeningococcal vaccine VAMENGOC-BC® that is produced on a large scale in Cuba, from which nearly 70 million doses have been applied in humans. 27 N. meningitidis OMVs are not only protective against meningitis, but also have well-known adjuvant properties associated with the stimulation of neutrophils, 28 bone marrow-derived dendritic cells 29 and macrophages, 30 which are key players of the innate immune system recognizing pathogen-associated molecular patterns through toll-like receptors (TLR). Stimulation of dendritic cells and macrophages induces the production of two proinflammatory cytokines IL-1β and IL18, serving as a bridge with the adaptive immune system.…”

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“…The evidence for a protective effect provided by the meningococcal VA-MENGOC-BC ® vaccine (Finlay Institute, Cuba) against N. gonorrhoeae was first reported in Cuba after the rapid decline in gonorrhea incidence following a vaccine campaign from 1988-1990 that targeted the highest-risk population (people aged 3 months to 24 years) [16,147,148]. The effectiveness of the vaccine against meningococcal disease was estimated to be between 81 and 83% after two doses, and the coverage for people under 24 years old was 95% [147]. VA-MENGOC-BC is a bivalent vaccine based on proteoliposome OMVs containing more than one hundred proteins from a hypervirulent MenB strain supplemented with meningococcal serogroup C polysaccharide [141,149].…”

“…VA-MENGOC-BC is a bivalent vaccine based on proteoliposome OMVs containing more than one hundred proteins from a hypervirulent MenB strain supplemented with meningococcal serogroup C polysaccharide [141,149]. Many conserved proteins between N. meningitidis and N. gonorrhoeae have been identified in the OMV component of the vaccine which could induce cross-reactive bactericidal antibodies against heterologous MenB strains and possibly against N. gonorrhoeae [16,147,150,151].…”