Pertactin-Deficient Bordetella pertussis, Vaccine-Driven Evolution, and Reemergence of Pertussis

Longhuan Ma; Amanda Caulfield; Kalyan K. Dewan; Eric T. Harvill


Emerging Infectious Diseases. 2021;27(6):1561-1566. 

In This Article


The rapid reemergence of pertussis noted in the early 2000s brought much initial speculation. Factors such as human migration, increased sensitivity of testing, increased volumes of testing, and reporting through heightened surveillance have been proposed to contribute to the observed resurgence.[1–3] However, the collective experience in countries switching from wP vaccines to aP vaccines strongly suggests that these safer, but less effective, vaccines have contributed to the resurgence of pertussis. In addition, the way multiple PRN-deficient strains have swept across countries that use aP vaccines presents a strong case in favor of vaccine-driven selection against PRN.[6–12] What has remained unclear is what will be the consequences of these changes. Will PRN-deficient strains continue to evolve, loosing other vaccine antigens until they escape vaccine effects completely? Or will the loss of these factors result in strains attenuated in virulence such that they become more like commensals than pathogens? Or is PRN really the only antigen that can be lost without serious fitness costs?

The 3 aspects of PRN we have highlighted for selective loss of PRN (i.e., its functional redundancy, the relatively longer functional persistence of antibodies against it, and its close location to the surface membrane for productive complement fixation) are not an exhaustive list of all possibilities and are not mutually exclusive. Sufficient sustained selective pressure against any particular antigen is likely to lead to its loss or change. Efforts to improve the current vaccine should be informed by a careful consideration of the lessons learned from this instance. If PRN is being lost because it is the only surface antigen, then should we replace it with 1 or more new surface antigens? If it is lost because its function is at least partly redundant then should we select some molecule(s) that is less likely to be redundant? In designing new vaccines, it would be prudent to carefully consider the issues that appear to be enabling potential vaccine escape mutants, such as PRN-deficient strains, to rapidly expand and rise to prominence.