Self-boosting vaccines and their implications for herd immunity

Abstract

Advances in vaccine technology over the past two centuries have facilitated far-reaching impact in the control of many infections, and today's emerging vaccines could likewise open new opportunities in the control of several diseases. Here we consider the potential, population-level effects of a particular class of emerging vaccines that use specific viral vectors to establish long-term, intermittent antigen presentation within a vaccinated host: in essence, "self-boosting" vaccines. In particular, we use mathematical models to explore the potential role of such vaccines in situations where current immunization raises only relatively short-lived protection. Vaccination programs in such cases are generally limited in their ability to raise lasting herd immunity. Moreover, in certain cases mass vaccination can have the counterproductive effect of allowing an increase in severe disease, through reducing opportunities for immunity to be boosted through natural exposure to infection. Such dynamics have been proposed, for example, in relation to pertussis and varicella-zoster virus. In this context we show how self-boosting vaccines could open qualitatively new opportunities, for example by broadening the effective duration of herd immunity that can be achieved with currently used immunogens. At intermediate rates of self-boosting, these vaccines also alleviate the potential counterproductive effects of mass vaccination, through compensating for losses in natural boosting. Importantly, however, we also show how sufficiently high boosting rates may introduce a new regime of unintended consequences, wherein the unvaccinated bear an increased disease burden. Finally, we discuss important caveats and data needs arising from this work.herpesvirus | waning immunity

Modeling infectious disease dynamics in the complex landscape of global health

“…potentially drawing on new data sources from social media (59,60), as well as for models that can capture national and nongovernmental motivations, interactions, and competition, economical or otherwise. Long-term control puts pathogens under strong selection for resistance, calling for evolution-proof control methods (61) and novel vaccine technologies and their optimized delivery (62). Finally, since the era of smallpox eradication, patterns of global disease circulation have changed radically.…”

Estimation of the Underlying Burden of Pertussis in Adolescents and Adults in Southern Ontario, Canada

“…Furthermore, widespread adoption of vaccination, but at a level insufficient to result in disease elimination, could eliminate natural “boosting” through interactions between previously infected individuals and infectious cases, further contributing to loss of immunity in older individuals [24], [25]. Indeed, a recent community-based study of cough illness performed in Poland suggested that pertussis in older adults might be under-reported by a factor of 167, in contrast to 4-fold under-reporting in children aged 3 to 5 [26].…”

Temporal evolution of immunity distributions in a population with waning and boosting

“…Recall the definition of τ > 0 in (2). The transport equation (8) with boundary condition (5) is solved along characteristics and we obtain…”

“…Laboratory analysis on vaccines tested on animals or humans suggest that the boosting efficacy might depend on several factors, among which the current immune status of the recovered host and the amount of pathogen he receives [1,13]. In previous mathematical models it was assumed that a boost restores the maximal immune status, the same as after natural infection [2]. Few authors have assumed that at each new contact with a known pathogen, the immune system is boosted a little, with a small increase in memory cells [11].…”