What Is Wrong with Pertussis Vaccine Immunity? The Problem of Waning Effectiveness of Pertussis Vaccines

Abstract

Pertussis is resurgent in some countries, particularly those in which children receive acellular pertussis (aP) vaccines in early infancy and boosters later in life. Immunologic studies show that, whereas whole-cell pertussis (wP) vaccines orient the immune system toward Th1/Th17 responses, acellular pertussis vaccines orient toward Th1/Th2 responses. Although aP vaccines do provide protection during the first years of life, the change in T-cell priming results in waning effectiveness of aP as early as 2-3 years post-boosters. Although other factors, such as increased virulence of pertussis strains, better diagnosis, and better surveillance may play a role, the increase in pertussis appears to be the result of waning immunity. In addition, studies in baboon models, requiring confirmation in humans, show that aP is less able to prevent nasopharyngeal colonization of Bordetella pertussis than wP or natural infection.

Figure 1.

(A) Demonstration of waning immunity following either infant/early childhood diphtheria, tetanus, and acellular pertussis (DTaP) or early adolescent tetanus, reduced diphtheria, and acellular pertussis (TdaP), measured as vaccine effectiveness. Vaccine effectiveness was calculated in each study as described in Table 1. The California five-dose study refers to Misegades et al. (2012), whereas the TdaP study refers to Klein et al. (2016). *Last point is 24–47 mo post-booster. (B) Demonstration of waning immunity with DTaP measured as relative risk (RR) of infection, with regard to first-year post-booster vaccination.

Figure 2.

New aP vaccine should be aimed to increase priming and boostability of current subunit vaccine through the addition of adjuvants that will program a more Th1/Th17 immune profile and possibly the addition of more subunit Ags inducing bactericidal activity to limit or prevent colonization. Another option, not mutually exclusive, is to deliver the vaccine and/or induce a stronger immune response to a more physiologically relevant compartment for the disease (i.e., the lung) to trigger more potent mucosal responses with hopefully a better duration as well through a better homing of memory cells in the lung mucosa. Several Ags, adjuvants, and/or routes of immunizations harboring the above properties have already been reported in the literature.