Abstract
SARS-CoV-2 vaccine clinical trials assess efficacy against disease (VEDIS), the ability to block symptomatic COVID-19. They only partially discriminate whether VEDIS is mediated by preventing infection completely, which is defined as detection of virus in the airways (VESUSC), or by preventing symptoms despite infection (VESYMP). Vaccine efficacy against transmissibility given infection (VEINF), the decrease in secondary transmissions from infected vaccine recipients, is also not measured. Using mathematical modeling of data from King County Washington, we demonstrate that if the Moderna (mRNA-1273QS) and Pfizer-BioNTech (BNT162b2) vaccines, which demonstrated VEDIS > 90% in clinical trials, mediate VEDIS by VESUSC, then a limited fourth epidemic wave of infections with the highly infectious B.1.1.7 variant would have been predicted in spring 2021 assuming rapid vaccine roll out. If high VEDIS is explained by VESYMP, then high VEINF would have also been necessary to limit the extent of this fourth wave. Vaccines which completely protect against infection or secondary transmission also substantially lower the number of people who must be vaccinated before the herd immunity threshold is reached. The limited extent of the fourth wave suggests that the vaccines have either high VESUSC or both high VESYMP and high VEINF against B.1.1.7. Finally, using a separate intra-host mathematical model of viral kinetics, we demonstrate that a 0.6 log vaccine-mediated reduction in average peak viral load might be sufficient to achieve 50% VEINF, which suggests that human challenge studies with a relatively low number of infected participants could be employed to estimate all three vaccine efficacy metrics.
Highlights
IntroductionThe endpoint for SARS-CoV-2 vaccine efficacy trials targeting licensure is vaccine efficacy against disease (VEDIS ), which is defined by a reduction in symptomatic disease, confirmed with polymerase chain reaction (PCR) testing for viral RNA, in vaccine recipients
High vaccine clinical trials assess efficacy against disease (VEDIS) is determined by a combination of two distinct phenomena which were only partially captured in these trials: vaccine efficacy against susceptibility (VESUSC ), which is defined as the vaccine-induced reduction in the rate of infection as evidenced by detection of virus by polymerase chain reaction (PCR), and vaccine efficacy against symptoms (VESYMP ) which is defined as the reduction in the presence of symptoms conditional on infection under vaccine versus placebo (Table 1, Figure 1) [1,2,10]
SARS-CoV-2 Inra-Host and Transmissions Models In Results Section 3.7, we used a separate set of models to estimate the viral load reduction required to achieve clinically relevant values for Vaccine efficacy against transmissibility given infection (VEINF) in a clinical trial
Summary
The endpoint for SARS-CoV-2 vaccine efficacy trials targeting licensure is vaccine efficacy against disease (VEDIS ), which is defined by a reduction in symptomatic disease, confirmed with polymerase chain reaction (PCR) testing for viral RNA, in vaccine recipients. High VEDIS is determined by a combination of two distinct phenomena which were only partially captured in these trials: vaccine efficacy against susceptibility (VESUSC ), which is defined as the vaccine-induced reduction in the rate of infection as evidenced by detection of virus by PCR, and vaccine efficacy against symptoms (VESYMP ) which is defined as the reduction in the presence of symptoms conditional on infection under vaccine versus placebo (Table 1, Figure 1) [1,2,10]. A vaccine that achieves high VEDIS via VESYMP could theoretically contribute less to overall herd immunity than a vaccine that achieves high VEDIS via VESUSC , as the former may not block ongoing chains of transmission from vaccine recipients
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