Immunogenicity and reactogenicity in UK infants of a novel meningococcal vesicle vaccine containing multiple class 1 (PorA) outer membrane proteins

Evidence for Naturally Acquired T Cell-Mediated Mucosal Immunity to Neisseria meningitidis

“…Men-B strain H44/76 (B:15:P1.7,16;L3,7,9), isogenic strains expressing different PorA types TR52 (B:15: P1.5,2), TR4 (B15:P1.7-8,4), TR10 (B: 15:P1.5-2,10), and a spontaneous PorA-negative mutant (B:15:P1.Ϫ,Ϫ) were kind gifts from the RIVM (The Netherlands) (34,35). Meningococcal OMV were prepared by deoxycholate detergent extraction (34,35) and were used at final concentrations of 0.1, 0.5, and 1.0 g protein/ml as indicated.…”

“…Meningococcal OMV were prepared by deoxycholate detergent extraction (34,35) and were used at final concentrations of 0.1, 0.5, and 1.0 g protein/ml as indicated. Final concentrations of 10 -20 g/ml keyhole limpet hemocyanin (KLH) Ag (Calbiochem CN Biosciences U.K., Beeston, U.K.), 100 ng/ml tetanus toxoid vaccine (TT; Aventis Pasteur MSD, Maidenhead, Berkshire, U.K.), and 30,000 endotoxin U/ml (8.3 g/ml) Escherichia coli 0111:B4 LPS (Sigma-Aldrich, Gillingham, U.K.) were used as controls.…”

Oral administration of recombinantNeisseria meningitidisPorA genetically fused toH. pyloriHpaA antigen increases antibody levels in mouse serum, suggesting that PorA behaves as a putative adjuvant

“…However, after a fourth dose in toddlers, a satisfactory immune response could be induced. 32,33 Another disadvantage of designing vaccines using purified PorA is that PorA behaves as a better antigen in its natural environment, i.e., the outer membrane. For instance, it has been reported that 96% of LPS is removed from PorA after PorA purification, and antibodies raised by OMV were bactericidal, but those raised by purified PorA were not.…”

Bexsero

“…13 To provide wider PorA-based protection, a dOMV vaccine based on two meningococcal strains each engineered to express three PorA proteins was developed and assessed in several clinical studies. 14,15 A broader SBA response was observed but was restricted to the six PorA subtypes represented. 16 The change in predominant clonal complexes and associated PorA subtypes, such as those seen in the UK isolates 17 suggest that a vaccine of this type would require periodic reformulation.…”