Murine monoclonal antibodies to PorA of Neisseria meningitidis show reduced protective activity in vivo against B : 15 : P1.7,16 subtype variants in an infant rat infection model

The major outer membrane protein PorA of Neisseria meningitidis is the targ et for bactericidal serosubtyping antibodies and is currently considered as a potential vaccine candidate against group B meningococcal disease. Altho ugh the minor antigenic variability of the PorA has been increasingly recog nized and described, its implication for vaccine design remains unclear. In this study, the protective activity of murine monoclonal PorA specific ant ibodies against four isogenic meningococcal P1.7,16 target strains, the pro totype P1.7,16a and three loop 4 point mutation variants (designated P1.7,1 6b to d) constructed from reference strain H44/76 (B:15:P1.7,16a), was eval uated in the infant rat infection model. All monoclonal antibodies had been obtained by immunization of mice with outer membrane protein preparations from meningococcal serosubtype P1.7,16 reference strain H44/76. A challenge dose of 10(5) cfu/pup was given i.p. 1-2 h after the i.p. injection of 1:1 00 diluted antibodies, and the development of bacteremia was assessed by cu lturing blood samples taken 6 h after challenge. MN14C11.6, a reference mon oclonal antibody for serosubtype P1.7 epitope located in predicted loop 1 ( VR1) identical in all the variants, was equally protective against all loop 4 variants. The three P1.16 specific monoclonal antibodies tested (MN5C11G , MN12H2 and 62D12-8) all completely protected animals against the prototyp e P1.7,16a, variably against the P1.7,16b and P1.7,16c, but not against the P1.7,16d variant. Our findings therefore suggest that certain subtype vari ants may escape protection in vivo conferred by PorA specific antibodies. ( C) 2001 Academic Press.