Modeling Fitness of Immune Evading Pertussis Mutants

Gowri Vadmal, a student at Stanford University, worked in the lab of Dr. Pej Rohani

Abstract Pertussis was considered one of the great diseases of childhood with most people experiencing a bout of the infection by the age of 15.  The initial roll out of vaccines in the 1950s led to a marked decline in pertussis incidence, with optimism over its potential elimination.  Over the past 20-30 years, however, a clear increasing trend in pertussis cases has emerged.  A number of putative Pertussis (whooping cough) is caused mainly by the bacterium Bordetella pertussis. Many countries use acellular pertussis vaccines containing the antigen pertactin (PRN), which plays an important role in pathogenesis. In recent years, we’ve observed an increasing number of B. pertussis isolates that are PRN-deficient and able to infect people even in highly vaccinated countries. We used SIRV models to look at the fitness cost of the bacterium losing PRN and the advantage of being able to infect already vaccinated people. Strains can invade the population only if their leakiness (ability to infect vaccinated people) and transmission are above the threshold for invasion, which depends on vaccination coverage and the cost of immune evasion for the strain. At low vaccination coverage, strains with high leakiness dominate the system when the fitness cost to evade immunity is low, but as cost increases for the strains to infect people, there is bistability between the wildtype and mutant strains. However, at higher vaccination coverage, the wild type completely fades out and the strains with the highest leakiness dominate the system. Thus, the conditions for B. pertussis mutant invasion can change depending on a population’s vaccine coverage, the cost of losing the pertactin gene, and the advantage of being able to evade vaccine immunity.