Pertactin negative Bordetella pertussis demonstrates higher fitness under vaccine selection pressure in a mixed infection model

Pertussis Vaccine Effectiveness in the Setting of Pertactin-Deficient Pertussis

“…18,35 The rapid increase in pertactindeficient B pertussis in multiple countries, combined with evidence that several mutations can result in lack of pertactin, suggest pertactin deficiency may confer a selective advantage to the bacteria. 22,[38][39][40][41] More specifically, several recent studies indicate pertactin deficiency may especially benefit the bacteria among a highly immunized population. For instance, pertactindeficient strains were found to colonize mice primed with acellular pertussis vaccine more effectively than pertactin-expressing strains; a separate study found that acellular vaccinated individuals had twoto fourfold greater odds of being infected with a pertactin-deficient 5 rather than a pertactin-expressing B pertussis strain.…”

“…21 Pertactin deficiency may have evolved in response to acellular vaccine-induced selection pressure, providing an advantage to the bacteria. 18,22 In 2012, an epidemic year for pertussis in the United States, Vermont reported the second highest pertussis incidence rate (103/100 000 population) in the country. 7 During this period, Vermont Department of Health Laboratory was one of a few laboratories in the nation that routinely cultured all specimens from suspected pertussis cases.…”

The History of Bordetella pertussis Genome Evolution Includes Structural Rearrangement

“…Although sequence diversity has also been observed in the vaccine immunogen pertactin (Prn), the circulating isolates recovered in the United States have become predominantly Prn deficient in recent years by one of at least 16 different mutations to the prn gene (16). The global emergence of Prn deficiency is well documented (16)(17)(18)(19), and deficiency may confer a fitness advantage during infection (20,21). While Prn deficiency appears to be more prevalent in isolates recovered from fully vaccinated patients, it does not appear to impact the effectiveness of acellular pertussis vaccines (22,23).…”

The role ofB. pertussisvaccine antigen gene variants in pertussis resurgence and possible consequences for vaccine development

“…However, in immunized mice, the reverse was observed, as the Prn-deficient strain accounted for over 90% of recovered bacteria by day 14. 16 Together these data very strongly suggest that the loss of expression of Prn generates a fitness advantage to B. pertussis, but only in hosts immunized with an ACV. This is compelling evidence to suggest that ACV-induced immunity generates a strong selection pressure on B. pertussis and in turn this suggests that this selection pressure has been the driver for the emergence of Prn-deficient B. pertussis strains.…”

“…15 Finally, a very recent study developed this further and assessed direct competition between Prn-expressing and Prn-deficient strains in the murine infection model. 16 Coinfection of na€ ıve mice and ACVimmunised mice with equal numbers of a Prn-expressing and a Prn-deficient strain revealed dramatic differences. In na€ ıve mice the Prn-expressing strain became dominant by day 3 post-inoculation and accounted for over 90% of the B. pertussis recovered by day 14, demonstrating a distinct fitness advantage from expression of Prn in these hosts.…”