Cross-Reactivity of Antibodies against PorA after Vaccination with a Meningococcal B Outer Membrane Vesicle Vaccine

Abstract

The cross-reactivity of PorA-specific antibodies induced by a monovalent P1.7-2,4 (MonoMen) and/or a hexavalent (HexaMen) meningococcal B outer membrane vesicle vaccine (OMV) in toddlers and school children was studied by serum bactericidal assays (SBA). First, isogenic vaccine strains and PorA-identical patient isolates were compared as a target in SBA, to ensure that the vaccine strains are representative for patient isolates. Geometric mean titers (GMTs) in SBA against patient isolates with subtypes P1.5-2,10 and P1.5-1,2-2 after vaccination with HexaMen were generally lower than those against vaccine strains with the same subtype, although the percentage of vaccine responders (>4-fold increase in SBA after vaccination) was not affected. Using various P1.7-2,4 patient isolates, GMTs as well as the number of vaccine responders were higher than for the P1.7-2,4 vaccine strain, indicating that the use of the P1.7-2,4 vaccine strain may have underestimated the immunogenicity of this subtype in HexaMen. Secondly, the cross-reactivity of antibodies induced by MonoMen and HexaMen was studied using several patient isolates that differed from the vaccine subtypes by having minor antigenic variants of one variable region (VR), by having a completely different VR or by having a different combination of VRs. MonoMen induced P1.4-specific antibodies that were crossreactive with P1.4 variants P1.4-1 and P1.4-3. HexaMen induced a broader cross-reactive antibody response against various patient isolates with one VR identical to a vaccine subtype or a combination of VRs included in HexaMen. Cross-reactivity, measured by a fourfold increase in SBA after vaccination, against these strains ranged from 23 to 92% depending on the subtype of the tested strain and was directed against both VR1 and VR2. The extended cross-reactivity of vaccinee sera induced by HexaMen against antigenic variants has important favorable implications for meningococcal B OMV vaccine coverage.

Comparison and Correlation of Neisseria meningitidis Serogroup B Immunologic Assay Results and Human Antibody Responses following Three Doses of the Norwegian Meningococcal Outer Membrane Vesicle Vaccine MenBvac

“…Interestingly, in the SBA assay, the phenotypically identical strain M01 240149 only had half the number of subjects attaining Ն4-fold increases, although the percentage of subjects with an SBA titer of Ն4 was similar. These findings are similar to previous reports wherein different P1.7-2,4 wild-type isolates have demonstrated significantly different SBA activity (13,44), suggesting that the standardization of strains between laboratories is crucial for the compatibility of the data. For the United Kingdom representative isolates, the SBA responses were generally poor, with low percentages of subjects achieving Ն4-fold increases.…”

Functional and Specific Antibody Responses in Adult Volunteers in New Zealand Who Were Given One of Two Different Meningococcal Serogroup B Outer Membrane Vesicle Vaccines

“…The variable regions 1 (VR1's) of the two PorA antigens (the P1.7-2 and P1.7 epitopes) are the same except for a deletion of three amino acids in P1.7-2, masking this epitope from interacting with a P1.7-specific monoclonal antibody (35,60), whereas the two VR2's (the P1.4 and P1.16 epitopes) are very different (35). Studies performed by the use of various antibody assays, including immunoblotting, have demonstrated that PorA antibodies induced by MenBvac, MeNZB, or the corresponding PorA components in the Dutch PorA OMV vaccines are mainly directed against VR2 in P1.7,16 and P1.7-2,4 PorA (26,34,42,55,62,63). The VR1 epitopes seem to be less immunogenic than VR2.…”

Stability of PorA during a Meningococcal Disease Epidemic

“…However, these researchers showed that there was no association between a low level of PorA expression and vaccination status, as there were equal numbers of meningococci expressing low levels of PorA in immunized and nonimmunized children. Vermont and colleagues (33) showed that immune responses directed against meningococci with significantly different porA VR2 sequences were reduced, whereas responses against isolates with porA variants that had most of the VR2-4 sequence conserved were less affected. Whether people challenged with meningococci demonstrating the P1.7-2,4 deletions or the transcriptional variations detected in this study would be protected by anti-P1.7-2,4 antibodies induced by a strain-specific vaccine cannot be determined from this study but is currently being investigated.…”