The VR2 Epitope on the PorA P1.7-2,4 Protein Is the Major Target for the Immune Response Elicited by the Strain-Specific Group B Meningococcal Vaccine MeNZB

Abstract

A protracted epidemic of group B meningococcal disease in New Zealand led to the testing of a strain-specific tailor-made vaccine, MeNZB. Immunogenicity levels achieved during age group trials enabled New Zealand's regulatory authority to grant licensure to deliver MeNZB to all individuals under age 20. During the trials target strains for serum bactericidal antibody measurements included the vaccine target strain NZ98/254 and two comparator epidemic-type strains (NZ94/167 and NZ02/09). In this study, 12 other strains differing variously from the vaccine strain by their capsular group, PorB type, and PorA variable region specificities, or PorA expression, were used as target strains. The PorA specificity of the serum bactericidal antibody responses to the vaccine was determined for 40 vaccinees. Sets of 10 pre- and postvaccination sera were chosen randomly from the young infant, older infant, toddler, and school-age group trials. Antibody recognition of linearized PorA proteins was also determined using immunoblotting. Across all age groups vaccine-induced serum bactericidal antibodies specifically targeted the VR2 P1.4 epitope of the PorA P1.7-2,4 protein irrespective of the PorB type and/or capsular type of the target strain. Deletion of amino acids within the VR2 epitope or replacement of the epitope through genetic exchange allowed strains variously to resist antibody-directed complement-mediated lysis and negated PorA-specific antibody recognition in immunoblots. The demonstration that the immunodominant antibody response was specifically for the VR2 P1.4 epitope of the PorA protein supports the public health decision to use a strain-specific vaccine for the control of New Zealand's epidemic of meningococcal disease.