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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.

Vaccine
|April 25, 2000
PubMed

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.

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