SARS-CoV-2 vaccine clinical trials assess efficacy against disease (VE DIS ), the ability to block symptomatic COVID-19. They only partially discriminate whether VE DIS is mediated by preventing infection completely, which is defined as detection of virus in the airways (VE SUSC ), or by preventing symptoms despite infection (VE SYMP ). Vaccine efficacy against transmissibility given infection (VE INF ), 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 VE DIS > 90% in clinical trials, mediate VE DIS by VE SUSC , 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 VE DIS is explained by VE SYMP , then high VE INF 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 VE SUSC or both high VE SYMP and high VE INF 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% VE INF, which suggests that human challenge studies with a relatively low number of infected participants could be employed to estimate all three vaccine efficacy metrics.
【저자키워드】 SARS-CoV-2, Vaccines, mathematical modeling, viral dynamics, 【초록키워드】 COVID-19, Efficacy, Vaccine, clinical trial, vaccine efficacy, Infection, clinical trials, Symptom, virus, SARS-CoV-2 vaccine, airway, BNT162b2, B.1.1.7 variant, Viral, Transmissibility, Viral load, mathematical model, B.1.1.7, symptomatic, herd immunity, viral kinetics, disease, Pfizer-BioNTech, Moderna, symptomatic COVID-19, Herd immunity threshold, Washington, airways, the vaccines, epidemic wave, Metrics, recipients, spring, average, secondary transmission, participant, limit, decrease, PROTECT, log, defined, predicted, explained, demonstrated, reached, the vaccine, reduction in, number of infected, mathematical, King, preventing infection, 【제목키워드】 modeling,