Pertussis immunity and epidemiology: mode and duration of vaccine-induced immunity

Abstract

SUMMARY The resurgence of pertussis in some countries that maintain high vaccination coverage has drawn attention to gaps in our understanding of the epidemiological effects of pertussis vaccines. In particular, major questions surround the nature, degree and durability of vaccine protection. To address these questions, we used mechanistic transmission models to examine regional time series incidence data from Italy in the period immediately following the introduction of acellular pertussis (aP) vaccine. Our results concur with recent animal-challenge experiments wherein infections in aP-vaccinated individuals proved as transmissible as those in naive individuals but much less symptomatic. On the other hand, the data provide evidence for vaccine-driven reduction in susceptibility, which we quantify via a synthetic measure of vaccine impact. As to the precise nature of vaccine failure, the data do not allow us to distinguish between leakiness and waning of vaccine immunity, or some combination of these. Across the range of well-supported models, the nature and duration of vaccine protection, the age profile of incidence and the range of projected epidemiological futures differ substantially, underscoring the importance of the remaining unknowns. We identify key data gaps: sources of data that can supply the information needed to eliminate these remaining uncertainties.

The impact of past vaccination coverage and immunity on pertussis resurgence

“…We examined three, not mutually exclusive, potential modes of failure (23–25): (1) Primary vaccine failure is the failure of the vaccine to “take” in some recipients, i.e., some fraction of those vaccinated receive full protection while the remainder receive none; (2) Failure in duration is the waning of vaccine-induced protection with time (26); (3) Failure in degree of protection, also known as vaccine “leakiness”, occurs when vaccine-induced protection is imperfect (22, 27), potentially due to antigenic evolution in the pathogen. We adopted the epidemiological structure proposed in (28) (fig. S1), which explicitly allows infections in naïve and vaccinated hosts to differ both in transmissibility and disease severity (and hence observability).…”

Vaccine impact in homogeneous and age-structured models

“…We begin with a brief discussion of the homogeneous model of an imperfect vaccine that was used in [9]. The model diagram is shown in Figure 1.…”

“…Vaccination has been one of our most successful tools in the battle against such diseases [12]. There have been many studies concerned with the effect of different types of infection- and vaccine-derived immunity on disease transmission [3,6,7,9–11,13]. McLean and Blower [11] introduced a quantity called the vaccine impact (here denoted by φ ), as a measure of the effectiveness of imperfect vaccines.…”

“…There have been many studies on the effects of modes of vaccine failure to the epidemiology of diseases [6,10,11]. In [9] we considered the following aspects of vaccine protection:…”

“…The fifth parameter (relative reporting probability) is important to include when fitting models to data, however it only affects the reporting of the disease and not the overall transmission of the disease. In [9] it was shown that the vaccine impact for an homogeneous model involving the five parameters is…”