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

Abstract

Recent reemergence of pertussis (whooping cough) in highly vaccinated populations and rapid expansion of Bordetella pertussis strains lacking pertactin (PRN), a common acellular vaccine antigen, have raised the specter of vaccine-driven evolution and potential return of what was once the major killer of children. The discovery that most circulating B. pertussis strains in the United States have acquired new and independent disruptive mutations in PRN is compelling evidence of strong selective pressure. However, the other 4 antigens included in acellular vaccines do not appear to be selected against so rapidly. We consider 3 aspects of PRN that distinguish it from other vaccine antigens, which might, individually or collectively, explain why only this antigen is being precipitously eliminated. An understanding of the increase in PRN-deficient strains should provide useful information for the current search for new protective antigens and provide broader lessons for the design of improved subunit vaccines.

Keywords: Bordetella pertussis; PRN; United States; acellular vaccine; antibody titers; bacteria; pertactin; pertactin deficient; pertussis; reemergence; respiratory infections; vaccine-driven evolution; vaccines; waning immunity; whole-cell vaccine; whooping cough.

Figure 1

Model for various roles of antibodies against antigens in acellular pertussis vaccine. A) Antibodies against PT and FHA neutralize secreted virulence factors and mitigate disease progression but are not targeted to the bacterial surface. B) Antibodies attaching to fimbriae poorly activate the complement system far from the bacterial membrane. C) Antibody-PRN complex induces strong bactericidal activity via multiple synergistic functions. This complex activates complement to form a MAC, activates complement to deposit components such as C3b that opsonize the bacterial surface, and binds FcRs on phagocytes to activate phagocytosis. PRN labels indicate strains specifically lacking PRN. Bp, Bordetella pertussis; CR1, complement receptor type 1; FcR, fragment crystallizable region; FHA, filamentous hemagglutinin; MAC, membrane attack complex; PRN, pertactin; PT, pertussis toxin.

Figure 2

Differential decay of antibodies against acellular pertussis vaccine antigens and their effective capacity for protection. Antibodies against PRN and FHA remain at relatively higher titers for a longer period. However, PT-specific antibodies decrease to low titers rapidly. A consistently low level of antibodies against FIM is induced. Solid lines indicate antibodies that have high protective capacity, and dotted lines indicate antibodies that had low protective capacity. Only PRN antibodies are highly protective and persist at high titers for years. FHA, filamentous hemagglutinin, FIM, fimbriae; PT, pertussis toxin; PRN, pertactin.