Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection
Top Cited Papers
- 17 May 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Medicine
- Vol. 27 (7), 1205-1211
- https://doi.org/10.1038/s41591-021-01377-8
Abstract
Predictive models of immune protection from COVID-19 are urgently needed to identify correlates of protection to assist in the future deployment of vaccines. 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. 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%). 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). 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. 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. 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.Funding Information
- Department of Health | National Health and Medical Research Council (GNT1173027, GNT1173528, GNT1123673, GNT2002073, GNT1149990, GNT1153493)
- Department of Health, Australian Government (MRF2005544, MRF2005544)
- State Government of Victoria
This publication has 60 references indexed in Scilit:
- Comparison of neutralizing and hemagglutination-inhibiting antibody responses for evaluating the seasonal influenza vaccineJournal of Virological Methods, 2012
- Hemagglutination Inhibition Antibody Titers as a Correlate of Protection for Inactivated Influenza Vaccines in ChildrenThe Pediatric Infectious Disease Journal, 2011
- Relationship between haemagglutination-inhibiting antibody titres and clinical protection against influenza: development and application of a bayesian random-effects modelBMC Medical Research Methodology, 2010
- Fast Implementation for Normal Mixed Effects Models With Censored ResponseJournal of Computational and Graphical Statistics, 2009
- Duration of Humoral Immunity to Common Viral and Vaccine AntigensThe New England Journal of Medicine, 2007
- A Framework for Assessing Immunological Correlates of Protection in Vaccine TrialsThe Journal of Infectious Diseases, 2007
- A model for immunological correlates of protectionStatistics in Medicine, 2005
- The time course of the immune response to experimental coronavirus infection of manEpidemiology and Infection, 1990
- Logistic-Normal Distributions: Some Properties and UsesBiometrika, 1980
- The role of serum haemagglutination-inhibiting antibody in protection against challenge infection with influenza A2 and B virusesEpidemiology and Infection, 1972