![]() ![]() In influenza infection, for example, a hemagglutination inhibition (HAI) titer of 1:40 is thought to provide 50% protection from influenza infection 7 (although estimates range from 1:17 to 1:110, refs. A defined correlate of protection will permit both confidence in opening up economies and facilitate rapid improvements in vaccines and immunotherapies. However, the duration of protective immunity is presently unclear, primary immune responses are inevitably waning 3, 4, 5, and there is ongoing transmission of increasingly concerning viral variants that may escape control by both vaccine-induced and convalescent immune responses 6.Ī critical challenge at present is to identify the immune correlate(s) of protection from SARS-CoV-2 infection and thereby predict how changes in immunity will be reflected in clinical outcomes. Seropositive recovered subjects have been estimated to have 89% protection from reinfection 1, and vaccine efficacies from 50 to 95% have been reported 2. Immunity to SARS-CoV-2 induced either through natural infection or vaccination has been shown to afford a degree of protection against reinfection and/or reduce the risk of clinically significant outcomes. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally over the past year, infecting an immunologically naive population and causing significant morbidity and mortality. Here, we show that neutralization level is highly predictive of immune protection, and provide an evidence-based model of SARS-CoV-2 immune protection that will assist in developing vaccine strategies to control the future trajectory of the pandemic. Neutralization titers against some SARS-CoV-2 variants of concern are reduced compared with the vaccine strain, and our model predicts the relationship between neutralization and efficacy against viral variants. Modeling of the decay of the neutralization titer over the first 250 d after immunization predicts that a significant loss in protection from SARS-CoV-2 infection will occur, although protection from severe disease should be largely retained. The estimated neutralization level required for 50% protection from severe infection was significantly lower (3% of the mean convalescent level 95% CI = 0.7–13%, P = 0.0004). We estimated the neutralization level for 50% protection against detectable SARS-CoV-2 infection to be 20.2% of the mean convalescent level (95% confidence interval (CI) = 14.4–28.4%). To address this, we analyzed the relationship between in vitro neutralization levels and the observed protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using data from seven current vaccines and from convalescent cohorts. ![]() Predictive models of immune protection from COVID-19 are urgently needed to identify correlates of protection to assist in the future deployment of vaccines. ![]()
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