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Effect of sequence variation in meningococcal PorA outer membrane protein on the effectiveness of a hexavalent PorA
S L Martin1, R Borrow, P van der Ley
1Meningococcal Reference Unit, Manchester Public Health Laboratory, Withington Hospital, Nell Lane, Manchester M20 2LR, UK.
Insights
A hexavalent PorA outer membrane vesicle vaccine shows promise for meningococcal serogroup B disease prevention. Antibody responses targeting specific variable regions, particularly VR2, were key to killing vaccine-resistant variants.
Area of Science:
- Microbiology
- Immunology
- Vaccinology
Background:
- Meningococcal serogroup C conjugate vaccines are available, but no vaccine exists for serogroup B.
- PorA outer membrane protein (OMP) is a potential vaccine candidate for serogroup B disease.
- A hexavalent PorA outer membrane vesicle (OMV) vaccine has shown promising results in early trials.
Purpose of the Study:
- To investigate the efficacy of a hexavalent PorA OMV vaccine against meningococcal serogroup B.
- To determine the role of antibody responses to specific PorA epitopes in vaccine-induced protection.
- To assess the impact of sequence variation in PorA variable regions on vaccine effectiveness.
Main Methods:
- Evaluation of a hexavalent PorA OMV vaccine in phase I and II clinical trials.
- Use of recombinant P1.5,10 PorA variants to assess antibody-mediated killing.
- Analysis of immune responses after three or four doses of the vaccine.
Main Results:
- The vaccine demonstrated significant killing of specific PorA variants, P1.10a and P1.10f, after multiple doses.
- Antibody induction targeting the VR2 epitope region was primarily responsible for the killing of the P1.10 serosubtype.
- A reduction in the killing of variants P1.10a and P1.10f was observed compared to the P1.10 strain.
Conclusions:
- The hexavalent PorA OMV vaccine shows potential for preventing meningococcal serogroup B disease.
- Antibody responses to specific PorA epitopes, particularly VR2, are crucial for vaccine efficacy.
- The significant sequence variation in PorA variable regions may impact the broad effectiveness of PorA-based vaccines.
Abstract:
Though meningococcal serogroup C conjugate vaccines have been introduced into the UK infant immunisation schedule, there is currently no vaccine solution for serogroup B disease. PorA outer membrane protein (OMP) is a potential serogroup B vaccine candidate. A hexavalent PorA outer membrane vesicle (OMV) vaccine has been evaluated in phase I and II trials with promising results. This vaccine contains six different PorA OMPs each representing a different serosubtype. However, considerable sequence variation occurs in the variable regions (VRs) encoding these serosubtypes. By using recombinant P1.5,10 PorA variants we have demonstrated that the killing of this particular serosubtype combination was due mainly to the induction of antibody to the VR2 (P1.10) epitope region, and that after three or four doses of vaccine there was a significant reduction in the killing of variants P1.10a (three doses, p<0.0001; four doses, p = 0.003) and P1.10f (three doses, p<0.0001; four doses, p = 0.002), as compared to responses to the P1.10 strain, when the P1.10 serosubtype was used as the immunogen. Since large numbers of serosubtype variants are known to exist, this finding may have implications for the use of PorA as a meningococcal serogroup B vaccine.