Vaccine-induced pathogen strain replacement: what are the mechanisms?

Abstract

Host immune systems impose natural selection on pathogen populations, which respond by evolving different antigenic signatures. Like many evolutionary processes, pathogen evolution reflects an interaction between different levels of selection; pathogens can win in between-strain competition by taking over individual hosts (within-host level) or by infecting more hosts (population level). Vaccination, which intensifies and modifies selection by protecting hosts against one or more pathogen strains, can drive the emergence of new dominant pathogen strains-a phenomenon called vaccine-induced pathogen strain replacement. Here, we review reports of increased incidence of subdominant variants after vaccination campaigns and extend the current model for pathogen strain replacement, which assumes that pathogen strain replacement occurs only through the differential effectiveness of vaccines against different pathogen strains. Based on a recent theoretical study, we suggest a broader range of possible mechanisms, some of which allow pathogen strain replacement even when vaccines are perfect-that is, they protect all vaccinated individuals completely against all pathogen strains. We draw an analogy with ecological and evolutionary explanations for competitive dominance and coexistence that allow for tradeoffs between different competitive and life-history traits.

Figure 1

Equilibrium prevalence as a function of vaccination rate for the system in appendix A. The figure assumes that vaccinated individuals are completely protected against both strains. Strain 1 dominates for vaccination rates between zero (no vaccination) and 1. For vaccination rates between 1 and 2 the two strains coexist. Strain 2 dominates for vaccination rates between 2 and 2.5. For higher vaccination rates, both strains are eliminated. The reproduction numbers of the strains in the absence of vaccination are respectively ${\mathcal{R}}_1(0)=4$ and ${\mathcal{R}}_2(0)=6$.

Figure 2

Invasion numbers as a function of vaccination rate: the case of superinfection. The figure assumes that vaccinated individuals are completely protected against both strains. Note that ${\hat{\mathcal{R}}}_1$ is a decreasing function, while ${\hat{\mathcal{R}}}_2$ is an increasing function. For ψ<1.1, the invasion reproduction numbers satisfy ${\hat{\mathcal{R}}}_1>1$ and ${\hat{\mathcal{R}}}_2<1$, so strain 1 will competitively exclude strain 2. For 1.1<ψ<1.75, the invasion reproduction numbers satisfy ${\hat{\mathcal{R}}}_1>1$ and ${\hat{\mathcal{R}}}_2>1$ and the two strains coexist. For ψ>1.75, the invasion reproduction numbers satisfy ${\hat{\mathcal{R}}}_1<1$ and ${\hat{\mathcal{R}}}_2>1$, so strain 2 prevails. The reproduction numbers in the absence of vaccination are $\mathcal{R}(0)=21.67$ and ${\mathcal{R}}_2(0)=28.167$.

Figure 3

Invasion numbers as a function of vaccination rate: the case of co-infection. The figure assumes that vaccinated individuals are completely protected against both strains. As before, ${\hat{\mathcal{R}}}_1$ is a decreasing function, while ${\hat{\mathcal{R}}}_2$ is an increasing function. For ψ<6, the invasion reproduction numbers satisfy ${\hat{\mathcal{R}}}_1>1$ and ${\hat{\mathcal{R}}}_2<1$, so strain 1 will competitively exclude strain 2. For 6<ψ<9, the invasion reproduction numbers satisfy ${\hat{\mathcal{R}}}_1>1$ and ${\hat{\mathcal{R}}}_2>1$ and the two strains coexist. For ψ>9, the invasion reproduction numbers satisfy ${\hat{\mathcal{R}}}_1<1$ and ${\hat{\mathcal{R}}}_2>1$, so strain 2 prevails. The reproduction numbers in the absence of vaccination are ${\mathcal{R}}_1(0)=25$ and ${\mathcal{R}}_2(0)=40$.

Figure 4

Strain replacement in a co-infection model without perfect asymmetry (Martcheva 2007). (a) Strain 1 dominates and strain 2 is eliminated in the absence of vaccination (ψ=0). (b) Strain 2 dominates while strain 1 is eliminated at vaccination rate ψ=12. With this vaccination rate, the fraction vaccinated in a disease-free population will be f=0.96. The reproduction numbers of the two strains in the absence of vaccination are ${\mathcal{R}}_1(0)=25$ and ${\mathcal{R}}_2(0)=31$.