RT Journal Article SR Electronic T1 Re-investigating the coughing rat model of pertussis to understand Bordetella pertussis pathogenesis JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.04.02.438291 DO 10.1101/2021.04.02.438291 A1 Jesse M. Hall A1 Jason Kang A1 Sophia M. Kenney A1 Ting Y. Wong A1 Graham J. Bitzer A1 Claire O. Kelly A1 Caleb A. Kisamore A1 Dylan T. Boehm A1 Megan A. DeJong A1 M. Allison Wolf A1 Emel Sen-Kilic A1 Alexander M. Horspool A1 Justin R Bevere A1 Mariette Barbier A1 F. Heath Damron YR 2021 UL http://biorxiv.org/content/early/2021/04/03/2021.04.02.438291.abstract AB Bordetella pertussis (Bp) is a highly contagious bacterium that is the causative agent of whooping cough (pertussis). Currently, acellular pertussis vaccines (aP; DTaP; Tdap) are used to prevent pertussis disease. However, it is clear that the aP vaccine efficacy quickly wanes, resulting in the re-emergence of pertussis. Furthermore, recent work performed by the CDC suggest that current circulating strains are genetically distinct from strains of the past. Emergence of genetically diverging strains combined with waning aP vaccine efficacy call for re-evaluation of current animal models of pertussis. In this study, we used the rat model of pertussis to compare two genetically divergent strains Tohama 1 and D420. We intranasally challenged seven-week-old Sprague-Dawley rats with 108 viable Tohama 1 and D420 and measured the hallmark signs/symptoms of Bp infection such as neutrophilia, pulmonary inflammation, and paroxysmal cough using whole body plethysmography. Onset of cough occurred between 2-4 days after Bp challenge averaging five coughs per fifteen minutes, with peak coughing occurring at day eight post infection averaging upward of thirteen coughs per fifteen minutes. However, we observed an increase of coughs in rats infected with clinical isolate D420 through 12 days post challenge. The rats exhibited increased bronchial restriction following Bp infection. Histology of the lung and flow cytometry confirm both cellular infiltration and pulmonary inflammation. D420 infection induced higher production of anti-Bp IgM antibodies compared to Tohama 1 infection. The coughing rat model provides a way of characterizing disease manifestation differences between Bp strains.