Heterologous prime-boost strategy to overcome weak immunogenicity of two serosubtypes in hexavalent Neisseria meningitidis outer membrane vesicle vaccine.

In the hexavalent meningococcal B OMV vaccine (HexaMen), two of the six Porin A proteins present are weakly immunogenic in mice and humans. We investigated the possibility that the lower immunogenicity of these serosubtypes (P1.7-2,4 and P1.19,15-1) could be overcome by using HexaMen and monovalent OMVs in heterologous immunisation protocols. Whereas HexaMen priming on day 0 followed by a monovalent P1.7-2,4 OMV boosting on day 28 (specific boost) did not result in higher titres against P1.7-2,4 (on day 42), the reverse order of immunisations (specific priming) resulted in significantly higher ELISA and SBA titres, but with lower avidity. For the strongly immunogenic PorA P1.5-1,2-2, all strategies gave high antibody responses, while avidity was highest after two monovalent P1.5-1,2-2 OMV immunisations. Based on the improved antibody titres obtained by specific priming with the weakly immunogenic PorA, we extended our study with combined P1.7-2,4 and P1.19,15-1 priming followed by two HexaMen booster immunisations. This resulted in higher ELISA and SBA titres against these weakly immunogenic PorAs, while the response against the other four PorAs was unaffected. Also, we observed an increase in antibody avidity using this schedule, indicating that affinity maturation has occurred. In conclusion, we found that specific priming, rather than specific boosting with monovalent OMVs, gave a significant rise in the serosubtype-specific immune response against a weakly immunogenic PorA, with high avidity antibodies in an extended immunisation schedule.