The Role of Virulence Proteins in Protection Conferred by Bordetella pertussis Outer Membrane Vesicle Vaccines

Abstract

The limited protective immunity induced by acellular pertussis vaccines demands development of novel vaccines that induce broader and longer-lived immunity. In this study, we investigated the protective capacity of outer membrane vesicle pertussis vaccines (omvPV) with different antigenic composition in mice to gain insight into which antigens contribute to protection. We showed that total depletion of virulence factors (bvg(-) mode) in omvPV led to diminished protection despite the presence of high antibody levels. Antibody profiling revealed overlap in humoral responses induced by vaccines in bvg(-) and bvg(+) mode, but the potentially protective responses in the bvg(+) vaccine were mainly directed against virulence-associated outer membrane proteins (virOMPs) such as BrkA and Vag8. However, deletion of either BrkA or Vag8 in our outer membrane vesicle vaccines did not affect the level of protection. In addition, the vaccine-induced immunity profile, which encompasses broad antibody and mixed T-helper 1, 2 and 17 responses, was not changed. We conclude that the presence of multiple virOMPs in omvPV is crucial for protection against Bordetella pertussis. This protective immunity does not depend on individual proteins, as their absence or low abundance can be compensated for by other virOMPs.

Naturally circulating pertactin-deficient Bordetella pertussis strains induce distinct gene expression and inflammatory signatures in human dendritic cells

“…LC–MS/MS proteomics analysis was performed as previously described [ 24 ], except that peptides were not chemically labelled. For peptide identification and corresponding proteins, MS/MS spectra were searched against the protein database of B. pertussis Tohama (NCBI 257313) (3258 entries) as previously applied [ 25 ].…”

Biological Nanoparticles in Vaccine Development

“…As mentioned, OMV-based vaccines currently exist for the prevention of Hib and MenB infections. Recent literature has focused on the development of OMV vaccines for influenza ( Rappazzo et al, 2016 ; Watkins et al, 2017b ), malaria ( Scaria et al, 2019 ), pertussis ( Raeven et al, 2020 ; Carriquiriborde et al, 2021 ), Lyme disease ( Klouwens et al, 2021 ), plague ( Carvalho et al, 2019 ; Wang X. et al, 2020 ), and SARS-Cov-2 ( Gaspar et al, 2021 ; Thapa et al, 2021 ; van der Ley et al, 2021 ). Due to the inherent flexibility and capability of the OMV platform, there is interest in expressing heterologous antigens from different pathogens on the same OMV to create novel combined vaccines ( König et al, 2021 ).…”

Bacterial Membrane Vesicles in Pneumonia: From Mediators of Virulence to Innovative Vaccine Candidates

“…Mechanistically, OMVs induced a combined T- and B-cell response ( Table 2 ), as demonstrated by a profound T h1 , T h2 , and T h17 response, and production of neutralizing antibodies and colonization of lung resident B- and T-cells [ 115 , 116 , 118 , 119 , 120 , 121 , 122 ]. Importantly, effective immunization by OMVs seems to depend on the presence of virulence proteins exposed on the vesicular surface, including pertussis toxin [ 123 , 124 ]. Accordingly, thorough testing for the safety of vaccine candidates is mandatory to exclude that OMV-associated toxins could confer harmful effects.…”