Variation in virulence between three representative <i>Bordetella pertussis</i> pertactin-negative clinical isolates

Pertussis is a respiratory disease caused by the bacterium <i>Bordetella pertussis</i>. Acellular pertussis (aP) vaccines replaced more reactogenic whole-cell pertussis (wP) vaccines in the United States in the 1990s. Despite high rates of vaccination, a slow but consistent increase in the number of U.S. pertussis cases was observed starting in the 1980s that accelerated following the introduction of aP vaccines. Most aP vaccines contain pertussis toxoid (PT), filamentous hemagglutinin (FHA), and pertactin (PRN), and some contain fimbriae (FIM 2/3). Countries that transitioned into aP vaccines have observed increasing rates of pertactin-negative (PRN^NEG) clinical isolates, exceeding 85% in some countries. This outcome suggests <i>B. pertussis</i> does not require PRN, and immune responses against PRN may impact <i>B. pertussis</i> circulation. With the high prevalence of PRN^NEG strains circulating in the United States, we sought to identify an acceptable PRN^NEG strain for use in baboon challenge studies and controlled human infection model (CHIM) studies. Baboons were challenged with the PRN-positive (PRN^POS) strain D420 or one of three PRN^NEG strains selected to represent the genetic diversity of <i>B. pertussis</i> strains circulating in the United States. Despite comparable levels of colonization between the animals infected with the PRN^NEG strains and D420, there was variability between the three PRN^NEG strains with respect to virulence, and two of the three strains appeared reduced in one or more measures of virulence. These findings suggest that some PRN^NEG clinical isolates may be less virulent than D420 and suggest care should be taken when selecting strains for baboon and CHIM studies.IMPORTANCEWith the increased circulation of <i>Bordetella pertussis</i> PRN^NEG strains in countries using acellular pertussis (aP) vaccines, understanding the epidemiology and pathogenesis of PRN^NEG strains is critical. Our results suggest that virulence varies between circulating PRN^NEG strains, with some strains appearing to be less virulent than PRN^POS strains. These results tell us that care should be taken when selecting PRN^NEG pertussis strains for baboon and CHIM studies. Our results may also support the continued use of PRN in aP vaccines. If PRN^NEG strains are less virulent and induce less severe disease than PRN^POS strains, maintaining vaccine selective pressure against PRN^POS strains may be beneficial.