A universal vaccine for the prevention of meningococcal meningitis in Africa

For more than years sub Saharan Africa has suffered with high rates of endemic meningococcal disease
and periodic epidemic epidemics involving over cases In a low cost serogroup A
polysaccharide protein conjugate vaccine MenAfriVac was introduced in the region The vaccine confers
protection against serogroup A MenA disease as well as asymptomatic nasopharyngeal MenA carriage but
has no effect on strains with other serogroups that also cause epidemics in the region Multivalent serogroup
A C Y and W conjugate vaccines are available in industrialized countries but are not affordable in Sub Sahara
which is one of the poorest regions of the world These vaccines also do not prevent disease from MenX
strains which also can cause epidemics in the region Recently two MenB vaccines based on Neisserial factor
H binding protein FHbp have been licensed in the US and Europe FHbp specifically binds human or non
human primate complement FH We are developing a novel native outer membrane vesicle NOMV vaccine
with genetically attenuated endotoxin and over expressed mutant FHbp with low FH binding NOMV FHbp In
a non human infant primate model a mutant recombinant FHbp antigen with two amino acid substitutions
elicited broader serum bactericidal antibody responses than the control FHbp vaccine that bound FH In
human FH transgenic mice our NOMV FHbp vaccine provided broader protection than a licensed multivalent
A C Y and W conjugate vaccine or the MenB vaccine developed by Novartis that contains FHbp that binds FH
However FHbp is variable with protein sequences falling into two sub families A and B Our prototype NOMV
FHbp vaccine only contained sub family B FHbp Our hypothesis is that including a second sub family A FHbp
in NOMV FHbp will result in a universal vaccine for Africa against strains with FHbp sub family A or B while
at the same time expanding coverage against MenB strains worldwide The goal of this Phase I proposal is
to produce a safe broadly protective affordable vaccine for use in preventing meningococcal disease
generally and in Africa specifically To accomplish this goal in Aim we will produce NOMV with over
expressed FHbp from both A and B sub families Immunogenicity will be evaluated in established transgenic
Tg mouse models expressing human FH and functional activity of elicited antibodies in complement mediated
serum bactericidal assays SBA which is an established correlate of protection against disease in humans In
Aim we will build upon the success of MenAfriVac by combining it with the new NOMV FHbp A B vaccine
The combined vaccine has the potential to ensure coverage against all of the predominant MenA strains while
at the same time suppressing the emergence of new pathogenic strains from other serogroups Project Narrative Relevance
Meningococcal disease is a major global health concern particularly in sub Saharan Africa which has periodic
epidemics involving hundreds of thousands of cases and tens of thousands of deaths Attempts to prevent
meningococcal disease in Sub Sahara have been confounded by emergence of strains not covered by the
existing serogroup A conjugate vaccine and high cost of multivalent capsular polysaccharide protein conjugate
vaccines which do not include serogroup X The goal of this project is to produce a novel safe effective and
affordable vaccine to prevent disease caused by all strains causing epidemics in Africa