Characterization of Human Bactericidal Antibodies toBordetella pertussis

Abstract

The Bordetella pertussis BrkA protein protects against the bactericidal activity of complement and antibody; however, some individuals mount an immune response that overcomes this bacterial defense. To further characterize this process, the bactericidal activities of sera from 13 adults with different modes of exposure toB. pertussis (infected as adults, occupational exposure, immunized with an acellular vaccine, or no identified exposure) against a wild-type strain and a BrkA complement-sensitive mutant were evaluated. All of the sera killed the BrkA mutant, suggesting past exposure to B. pertussis or cross-reactive organisms. Several samples had no or minimal activity against the wild type. All of the sera collected from the infected and occupationally exposed individuals but not all of the sera from vaccinated individuals had bactericidal activity against the wild-type strain, suggesting that some types of exposure can induce an immune response that can overcome the BrkA resistance mechanism. Adsorbing serum with the wild-type strain removed the bactericidal antibodies; however, adsorbing the serum with a lipopolysaccharide (LPS) mutant or an avirulent (bvg mutant) strain did not always result in loss of bactericidal activity, suggesting that antibodies to either LPS orbvg-regulated proteins could be bactericidal. All the samples, including those that lacked bactericidal activity, contained antibodies that recognized the LPS of B. pertussis. Bactericidal activity correlated best with the presence of the immunoglobulin G3 (IgG3) antibodies to LPS, the IgG subtype that is most effective at fixing complement.

Mutants in the ptlA-H genes of Bordetella pertussis are deficient for pertussis toxin secretion

“…B. pertussis cells from the secretion assay were concentrated to an OD 600 of 16 in PBS and 10 Wlsamples subjected to SDS-PAGE, transferred and visualized as previously described [8]. Gels were probed with antibodies against PtlF [9].…”

Chemical Synthesis and Immunological Evaluation of a Pentasaccharide Bearing Multiple Rare Sugars as a Potential Anti‐pertussis Vaccine

“…[15] Unlike antibodies against the exotoxins such as pertussis toxin, anti-LPS IgG antibodies can confer complement-dependent cytotoxicity against B. pertussis. [16] Thea ntibodies could also overcome pertussissresistance to bactericidal activities. [16] In addition, studies have shown that the LPS structure is highly conserved across various B. pertussis strains and does not change in clinical isolates from pre-and post-vaccine era, [17] rendering it attractive for broad spectrum anti-pertussis vaccine development.…”

Chemical Synthesis and Immunological Evaluation of a Pentasaccharide Bearing Multiple Rare Sugars as a Potential Anti‐pertussis Vaccine

“…LPS can induce nitric oxide production and contribute to disease pathology by damaging respiratory ciliated cells . Unlike antibodies against the exotoxins such as pertussis toxin, anti‐LPS IgG antibodies can confer complement‐dependent cytotoxicity against B. pertussis . The antibodies could also overcome pertussis's resistance to bactericidal activities .…”

“…Unlike antibodies against the exotoxins such as pertussis toxin, anti‐LPS IgG antibodies can confer complement‐dependent cytotoxicity against B. pertussis . The antibodies could also overcome pertussis's resistance to bactericidal activities . In addition, studies have shown that the LPS structure is highly conserved across various B. pertussis strains and does not change in clinical isolates from pre‐ and post‐vaccine era, rendering it attractive for broad spectrum anti‐pertussis vaccine development.…”