Expression of an inaccessible P1.7 subtype epitope on meningococcal class 1 proteins

Abstract

Summary. Dot-blot analysis of whole-cell suspensions of meningococci showed that 8 1 O h of B : 15 : P1.16 strains from patients reacted with a monoclonal antibody (MAb) against subtype PI .7. The remaining strains, which did not react on dot-blots or in ELISA, demonstrated the P1.7 subtype epitope on immunoblots after denaturation of the cells with sodium dodecyl sulphate. The monomeric class 1 proteins of the two P1.16 subtype variants had slightly different mol. wts, but bound the PI .7 antibody equally well. These results were explained by a deletion of three codons in the gene encoding the first variable region of the P 1.16 class 1 protein. The deletion accounted for the non-exposure of the P1.7 epitope on native cells. Other patient strains, with subtypes P1.3, P1.9 or without any known subtype, also showed a binding site for the P1.7 MAb, which became available only after denaturation. Demonstration of inaccessible epitopes may have consequences for subtype designations and vaccine development.

Clonal Distribution of Invasive Neisseria meningitidis Serogroup C Strains Circulating from 1976 to 2005 in Greater São Paulo, Brazil

“…Out of the 122 NST isolates, 59 (48.3%) had PorA VR2 type P1.14-6, 49 (40.2%) had PorA types other than P1.14-6 for which there are no currently available MAbs, and for the remaining 14 (11.5%) isolates we were not able to amplify the porA gene. Out of the 59 NST isolates with PorA VR type P1.14-6, only 10 expressed PorA on SDS-PAGE gels and reacted with MAb P1.14-6 on immunoblots; this is a typical characteristic of some already-described PorA masked epitopes (44). MLST and 16S rRNA gene typing.…”

Neisseria meningitidis Native Outer Membrane Vesicles Containing Different Lipopolysaccharide Glycoforms as Adjuvants for Meningococcal and Nonmeningococcal Antigens

“…This might be due to the same VR1 family being present in both sequences. However, P1.7-2 is a shorter VR1 sequence, also referred to as a masked or inaccessible subtype epitope, because it only becomes available to the P1.7 monoclonal antibody when it is denatured (40). Most SBA activity against PorA P1.7-2,4 is thus thought to be directed against the VR2 P1,4 sequence.…”

Current status of meningococcal group B vaccine candidates: capsular or noncapsular?

“…Considerable variation in their level of expression exists, and the expression rate can sometimes be reduced during the course of an infection (66,107 (18,152). Initially, these epitopes appeared to be linear in nature and inaccessible to specific antibodies in the intact cells of some strains (227), but the most recent studies using cyclic peptides point to the conformational nature of the class 1 epitopes (39). Although antibodies to class 1 proteins were protective in the newborn rat model mentioned above, this protection appeared to be type specific (185).…”