Identification of immunogenic outer membrane vesicle vaccine antigen components using a meningococcal protein microarray

Abstract

Outer membrane vesicle (OMV)-based vaccines have been employed worldwide in response to epidemic meningococcal disease outbreaks caused by Neisseria meningitidis. The complex composition of OMVs raises challenges in the identification of antigens which contribute to a protective immune response. Here, we measured total IgG antibody binding profiles to a dedicated antigen microarray using human sera from an open-label Phase II trial (NCT00962624) of 4CMenB (Bexsero), a licensed vaccine containing an OMV component. Significant IgG responses were observed against specific Outer Membrane Proteins (OMPs) from OMV antigens, including FetA, PorB, BamA and PorA. Partial Least Squares Regression was used to correlate IgG antibody reactivity profiles with the human complement-dependent killing of meningococci. We show that this approach is a powerful method to identify the potential contributions of OMV antigens - notably OpcA, FetA, PorA and PorB- towards serum bactericidal activity in human vaccinee serum against indicator strains, a recognised correlate of protection against invasive meningococcal disease.

Keywords: Antigen microarray; Bexsero; Meningococcal disease; Neisseria meningitidis; Outer membrane vesicles (OMVs); Partial least squares regression (PLS); Vaccine antigens.