Influence of serogroup B meningococcal vaccine antigens on growth and survival of the meningococcus in vitro and in ex vivo and in vivo models of infection.
A novel vaccine against serogroup B meningococcal disease - containing a combination of protein antigens identified by reverse vaccinology: fHBP fused to GNA2091, GNA2132 fused to GNA1030, and NadA - is currently in Phase III clinical trials. In order to determine the role of these antigens in the growth, survival and fitness of the meningococcus, we generated a mutant lacking the expression of all five protein antigens (5KO), a mutant lacking the three main antigens (fHBP, GNA2132 and NadA; 3KO), as well as strains lacking the single antigens. Our results show that abrogation of expression of these antigens in Neisseria meningitidis results in reduced growth in vitro, increased sensitivity of the bacterium to stresses it may encounter in the host, as well as reduced fitness in ex vivo models of infection and in an in vivo infant rat competitive index assay. These results support a multivalent vaccine approach, which was undertaken to strengthen the protective activity of the vaccine antigens, increase the breadth of MenB strains targeted by the vaccine, and limit the potential for selection of vaccine escape mutants.
Seib
Kate L
KL
Novartis Vaccines, Via Fiorentina 1, 53100 Siena, Italy. kate.seib@novartis.com <kate.seib@novartis.com>
Oriente
Francesca
F
Adu-Bobie
Jeannette
J
Montanari
Paolo
P
Ferlicca
Francesca
F
Giuliani
Marzia M
MM
Rappuoli
Rino
R
Pizza
Mariagrazia
M
Delany
Isabel
I
D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000502:physiology*; D018533:Biomass; D001770:Blood Bactericidal Activity; D002986:Clinical Trials as Topic; D015169:Colony Count, Microbial; D017353:Gene Deletion; D006801:Humans; D022401:Meningococcal Vaccines / Q000276:immunology; D050296:Microbial Viability; D016254:Mutagenesis, Insertional; D038541:Neisseria meningitidis, Serogroup B / Q000235:genetics / Q000472:pathogenicity*; D009391:Nephelometry and Turbidimetry; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological; D014774:Virulence
D000942:Antigens, Bacterial; D022401:Meningococcal Vaccines