Immunoproteomic Profiling of Bordetella pertussis Outer Membrane Vesicle Vaccine Reveals Broad and Balanced Humoral Immunogenicity

The
current resurgence of whooping cough is alarming, and improved
pertussis vaccines are thought to offer a solution. Outer membrane
vesicle vaccines (omvPV) are potential vaccine candidates, but omvPV-induced
humoral responses have not yet been characterized in detail. The purpose
of this study was to determine the antigen composition of omvPV and
to elucidate the immunogenicity of the individual antigens. Quantitative
proteome analysis revealed the complex composition of omvPV. The omvPV
immunogenicity profile in mice was compared to those of classic whole
cell vaccine (wPV), acellular vaccine (aPV), and pertussis infection.
Pertussis-specific antibody levels, antibody isotypes, IgG subclasses,
and antigen specificity were determined after vaccination or infection
by using a combination of multiplex immunoassays, two-dimensional
immunoblotting, and mass spectrometry. The vaccines and infection
raised strong antibody responses, but large quantitative and qualitative
differences were measured. The highest antibody levels were obtained
by omvPV. All IgG subclasses (IgG1/IgG2a/IgG2b/IgG3) were elicited
by omvPV and in a lower magnitude by wPV, but not by aPV (IgG1) or
infection (IgG2a/b). The majority of omvPV-induced antibodies were
directed against Vag8, BrkA, and LPS. The broad and balanced humoral
response makes omvPV a promising pertussis vaccine candidate.