Epidemiological and evolutionary considerations of SARS-CoV-2 vaccine dosing regimes.

Chadi M Saad-Roy,Michael J Mina,C Jessica E Metcalf,Sinead E Morris,Jeremy Farrar,Bryan T Grenfell,Oliver G Pybus,Rachel E Baker,Andrea L Graham,Caroline E Wagner,Edward C Holmes,Simon A Levin

doi:10.1126/science.abg8663

Abstract

Given vaccine dose shortages and logistical challenges, various deployment strategies are being proposed to increase population immunity levels to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Two critical issues arise: How timing of delivery of the second dose will affect infection dynamics and how it will affect prospects for the evolution of viral immune escape via a buildup of partially immune individuals. Both hinge on the robustness of the immune response elicited by a single dose as compared with natural and two-dose immunity. Building on an existing immuno-epidemiological model, we find that in the short term, focusing on one dose generally decreases infections, but that longer-term outcomes depend on this relative immune robustness. We then explore three scenarios of selection and find that a one-dose policy may increase the potential for antigenic evolution under certain conditions of partial population immunity. We highlight the critical need to test viral loads and quantify immune responses after one vaccine dose and to ramp up vaccination efforts globally.

Highlights

As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) betacoronavirus (β-CoV) pandemic continues, the deployment of safe and effective vaccines presents a key intervention for mitigating disease severity and spread and eventually relaxing non-pharmaceutical interventions (NPIs)
When one dose vaccinal immunity is poor, a one-dose strategy results in the rapid accumulation of partially susceptible SS1 individuals (Fig. 4B, bottom row) and a greater infection burden. (Note, this SS1 immune class is highlighted in orange for visibility in Figs. 1, 2, and 4.) When the assumed individual rates of evolutionary adaptation arising from these infection classes are high (Scenarios II and III), we find that a one-dose strategy could lead to substantially higher relative rates of adaptation
We have shown that different regimes may have crucial epidemiological and evolutionary impacts, resulting in a wide range of potential outcomes in the medium term

Summary

Introduction

As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) betacoronavirus (β-CoV) pandemic continues, the deployment of safe and effective vaccines presents a key intervention for mitigating disease severity and spread and eventually relaxing non-pharmaceutical interventions (NPIs). The first two elicit adaptive immunity against SARS-CoV-2 in response to the introduction of messenger ribonucleic acid (mRNA) molecules that encode the spike protein of SARSCoV-2 [2], and appear to offer greater than 95% (Pfizer/BioNTech [3], approved in 60 countries) and 94% (Moderna [2], approved in 38 countries) protection against symptomatic coronavirus disease 2019 (COVID-19). Both of these mRNA vaccines were tested in clinical trials according to a two-dose regime with dose spacing of 21 and 28 days for the Pfizer/BioNTech and Moderna platforms, respectively.

Methods

Findings

Conclusion