Antibodies binding diverse pertactin epitopes protect mice from Bordetella pertussis infection

J Biol Chem. 2022 Mar;298(3):101715. doi: 10.1016/j.jbc.2022.101715. Epub 2022 Feb 11.

Abstract

Infection by the bacterium Bordetella pertussis continues to cause considerable morbidity and mortality worldwide. Many current acellular pertussis vaccines include the antigen pertactin, which has presumptive adhesive and immunomodulatory activities, but is rapidly lost from clinical isolates after the introduction of these vaccines. To better understand the contributions of pertactin antibodies to protection and pertactin's role in pathogenesis, we isolated and characterized recombinant antibodies binding four distinct epitopes on pertactin. We demonstrate that four of these antibodies bind epitopes that are conserved across all three classical Bordetella strains, and competition assays further showed that antibodies binding these epitopes are also elicited by B. pertussis infection of baboons. Surprisingly, we found that representative antibodies binding each epitope protected mice against experimental B. pertussis infection. A cocktail of antibodies from each epitope group protected mice against a subsequent lethal dose of B. pertussis and greatly reduced lung colonization levels after sublethal challenge. Each antibody reduced B. pertussis lung colonization levels up to 100-fold when administered individually, which was significantly reduced when antibody effector functions were impaired, with no antibody mediating antibody-dependent complement-induced lysis. These data suggest that antibodies binding multiple pertactin epitopes protect primarily by the same bactericidal mechanism, which overshadows contributions from blockade of other pertactin functions. These antibodies expand the available tools to further dissect pertactin's role in infection and understand the impact of antipertactin antibodies on bacterial fitness.

Keywords: Bordetella; acellular vaccine; bactericidal antibodies; phage display; virulence factors; whooping cough.

MeSH terms

  • Animals
  • Antibodies* / immunology
  • Antibodies, Bacterial / immunology
  • Bacterial Outer Membrane Proteins* / chemistry
  • Bacterial Outer Membrane Proteins* / immunology
  • Bacterial Outer Membrane Proteins* / metabolism
  • Bordetella pertussis*
  • Epitopes
  • Mice
  • Pertussis Vaccine / immunology
  • Virulence Factors, Bordetella* / chemistry
  • Virulence Factors, Bordetella* / immunology
  • Virulence Factors, Bordetella* / metabolism
  • Whooping Cough* / prevention & control

Substances

  • Antibodies
  • Antibodies, Bacterial
  • Bacterial Outer Membrane Proteins
  • Epitopes
  • Pertussis Vaccine
  • Virulence Factors, Bordetella
  • pertactin