Targeted vaccination and the speed of SARS-CoV-2 adaptation

Abstract

The limited supply of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) raises the question of targeted vaccination. Many countries have opted to vaccinate older and more sensitive hosts first to minimize the disease burden. However, what are the evolutionary consequences of targeted vaccination? We clarify the consequences of different vaccination strategies through the analysis of the speed of viral adaptation measured as the rate of change of the frequency of a vaccine-adapted variant. We show that such a variant is expected to spread faster if vaccination targets individuals who are likely to be involved in a higher number of contacts. We also discuss the pros and cons of dose-sparing strategies. Because delaying the second dose increases the proportion of the population vaccinated with a single dose, this strategy can both speed up the spread of the vaccine-adapted variant and reduce the cumulative number of deaths. Hence, strategies that are most effective at slowing viral adaptation may not always be epidemiologically optimal. A careful assessment of both the epidemiological and evolutionary consequences of alternative vaccination strategies is required to determine which individuals should be vaccinated first.

Keywords: COVID-19; SARS-CoV-2; adaptation; evolutionary epidemiology; vaccination.

Fig. 1.

Scenario 1: heterogeneity in contact numbers and vulnerability. (A) A graphical presentation of the epidemiological life cycle with L hosts who are more vulnerable to the disease and H hosts who have a higher number of contacts. Infected hosts are indicated with a light red shading, and vaccination is indicated with a bold circle border. The force of infection on naive hosts is noted ${\mathrm{\Lambda }}_i=h_i+{\widehat{h}}_i$ (see Materials and Methods and Table 1 for additional details on this model). (B) Dynamical change of the frequency p_m of the vaccine-adapted mutant for two distinct targeted vaccination strategies: 1) mostly L hosts are vaccinated (blue lines) and 2) mostly H hosts are vaccinated (red lines). The full lines indicate the exact numerical computation, and the dashed lines indicate the approximation obtained from Eq. 2. The gray areas indicate the period where NPI were used to control the epidemic ($c(t)=0.7$ with NPI). (C) Incidence of the epidemic (fraction of the total host population that is infected) in the absence of vaccination (dotted black line) or under the two alternative vaccination strategies used in B (blue and red lines). (D) Cumulative number of deaths (fraction of the total host population) in the absence of vaccination (dotted black line) or under the two alternative vaccination strategies used in B (blue and red lines).

Fig. 2.

Scenario 2: heterogeneity in the number of vaccination doses. (A) A graphical presentation of the epidemiological life cycle where the superscripts I and II refer to the first and second doses of vaccine. Infected hosts are indicated with a light red shading, and vaccination is indicated with a bold circle border. The force of infection on naive hosts is noted ${\mathrm{\Lambda }}_i=h_i+{\widehat{h}}_i$ (see Materials and Methods and Table 2 for additional details on this model). (B) Dynamical change of the frequency p_m of the vaccine-adapted mutant for two distinct targeted vaccination strategies: 1) vaccinated hosts receive two doses sequentially (purple lines) and 2) a single dose is used for each host (orange lines). The full lines indicate the exact numerical computation, and the dashed lines indicate the approximation obtained from Eq. 3. The gray areas indicate the period where NPI were used to control the epidemic ($c(t)=0.7$ with NPI). (C) Incidence of the epidemic (fraction of the total host population that is infected) in the absence of vaccination (dotted black line) or under the two alternative vaccination strategies used in B (purple and orange lines). (D) Cumulative number of deaths (fraction of the total host population) in the absence of vaccination (dotted black line) or under the two alternative vaccination strategies used in B (purple and orange lines).