First report and detailed characterization of B. pertussis isolates not expressing pertussis toxin or pertactin

Bouchez, Valérie; Brun, Delphine; Cantinelli, Thomas; Dore, Gregory J.; Njamkepo, Elisabeth; Guiso, Nicole

doi:10.1016/j.vaccine.2009.07.074

Cited by 157 publications

(183 citation statements)

References 29 publications

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“…All procedures involving animals were conducted in accordance with the Institut Pasteur Animal Care and Use Committee guidelines. LD 50 determinations were conducted as described elsewhere (Bouchez et al, 2009). …”

Section: Lysis Inhibition (%) = − Isolate Lysis Isolate Lysis With Serummentioning

confidence: 99%

Antibody-mediated inhibition of Bordetella pertussis adenylate cyclase–haemolysin-induced macrophage cytotoxicity is influenced by variations in the bacterial population

Hégerlé

Guiso

2014

Microbiology

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Whooping cough is a vaccine-preventable disease presenting with epidemic cycles linked to natural and/or vaccine-driven evolution of the aetiological agent of the disease, Bordetella pertussis. Adenylate cyclase-haemolysin (AC-Hly) is a major toxin produced by this pathogen, which mediates macrophage apoptosis in vitro and in vivo. While current acellular pertussis vaccine (APV) formulations do not include AC-Hly, they all contain pertussis toxin and can comprise filamentous haemagglutinin (FHA), which interacts with AC-Hly, and pertactin (PRN), which has been hypothesized also to interact with AC-Hly. We aimed to study the capacity of specific antibodies to inhibit the in vitro B. pertussis AC-Hly-mediated cytotoxicity of J774A.1 murine macrophages in a background of a changing bacterial population. We demonstrate that: (i) clinical isolates of different types or PRN phenotype are all cytotoxic and lethal in the mouse model of respiratory infection; (ii) lack of PRN production does not impact AC-Hly-related phenotypes; (iii) anti-AC-Hly antibodies inhibit cell lysis whatever the phenotype of the isolate, while anti-PRN antibodies significantly inhibit cell lysis provided the isolate produces this antigen, which might be relevant in vivo for APV-induced immunity; and (iv) anti-FHA antibodies only inhibit lysis induced by isolates collected in 2012, maybe indicating specific characteristics of epidemic lineages of B. pertussis.

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Section: Lysis Inhibition (%) = − Isolate Lysis Isolate Lysis With Serummentioning

confidence: 99%

Antibody-mediated inhibition of Bordetella pertussis adenylate cyclase–haemolysin-induced macrophage cytotoxicity is influenced by variations in the bacterial population

Hégerlé

Guiso

2014

Microbiology

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“…The fact that new variant B. pertussis strains are more often isolated from vaccinated than from nonvaccinated patients further supports this notion [45,46]. Immune pressure on B. pertussis antigens can eventually even result in functional inactivation or entire deletion of the genes coding for them, as has been described for ptx and prn [45].…”

Section: Teenagers/ Adolescentsmentioning

confidence: 64%

“…Prn deficiency does not seem to be such a rare phenomenon. In France, Bouchez et al noted that a significant percentage (5.6%) of the strains from studied hospitalized newborns below 6 months of age did not produce Prn [45]. Recently, Otsuka et al reported that Prn-deficient strains have significantly increased in B. pertussis populations since the early 2000s in Japan [47].…”

Section: Teenagers/ Adolescentsmentioning

confidence: 99%

“…However, adaptation may also affect strain virulence properties or the biological impact of antigens, as is under investigation by several research groups. In preliminary studies, Prn-deficient strains were found to have competing growth advantage in vitro [47], but reduced multiplication in adult mice [45]. By producing 1.6-times more of the virulence factor and immune-modulating agent, Ptx, the emerging ptxP3 strains may alter the course or severity of an infection before the immune response can become effective [41].…”

Section: Teenagers/ Adolescentsmentioning

confidence: 99%

“…Antibody or T-cell cross reactivity between allelic variants of Ptx S1, Prn and fimbriae may still ensure protection, depending on the absolute level of the memory response, but loss of entire expression of important vaccine antigens such as Ptx and/or Prn in circulating strains will unambiguously narrow the effective breadth of the recall response [45].…”

Section: Mechanisms Underlying Progressive Loss Of Protective Immunitmentioning

confidence: 99%

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