Immune Correlates of Protection in SARS-CoV-2 Vaccination
Summary
Immune correlates of protection encompass measurable immune responses that predict vaccine-induced efficacy against SARS-CoV-2 infection and disease. Central to these correlates are humoral markers, notably neutralising antibody titres and binding antibody levels directed at the viral spike protein or its receptor binding domain, which exhibit strong quantitative relationships with risk reduction for symptomatic and severe COVID-19. Cellular immunity, including T-cell responses, complements humoral markers by contributing to the durability and breadth of protection, particularly against emerging variants. Defining threshold levels of these markers enables immunobridging for new vaccine candidates, informs booster timing, and supports global vaccine licensure and distribution strategies. The global significance of these findings lies in their application to optimise vaccine deployment, tailor booster campaigns in vulnerable populations and adapt formulations to antigenic shifts in circulating variants.
Research from Nature Portfolio
A 2023 meta-analysis of vaccine efficacy studies demonstrated that predicted neutralising antibody titres, based on regimen, time since vaccination and variant lineage, correlate strongly with observed protection against symptomatic and severe COVID-19. This work quantified the impact of antibody waning and variant-driven escape on predicted vaccine effectiveness, reinforcing the central role of neutralising titres as a mechanistic correlate.
In the PREVENT-19 phase 3 trial, quantitative measures of post-dose-two spike and RBD IgG, alongside pseudovirus neutralising antibody ID50, were inversely associated with breakthrough risk. Vaccine efficacy rose from approximately 76% at low neutralisation titres to over 96% at high titres, underscoring the utility of these markers for cross-platform immunobridging and regulatory decision-making.
A large observational study in the United Kingdom compared anti-spike IgG trajectories following two doses of ChAdOx1-nCoV-19 or BNT162b2. Higher peak and more sustained antibody levels were observed with BNT162b2, translating to longer duration of protection. Prior infection boosted both peak levels and half-life of antibodies, emphasising the contribution of hybrid immunity and the need for targeted booster policies.
Immune Correlates of Protection in SARS-CoV-2 Vaccination publication trend
The graph below shows the total number of articles in immune correlates of protection in sars-cov-2 vaccination across all publications each year (not limited to Nature Index journals).
Technical terms
Neutralising antibody titre: The reciprocal dilution of serum achieving a defined percentage inhibition of viral infection in vitro, reflecting functional antibody potency.
Binding antibody: Antibodies quantified by their capacity to bind viral antigens, typically measured by enzyme-linked assays without direct assessment of viral neutralisation.
Correlate of protection: An immune parameter statistically linked to the degree of clinical protection afforded by vaccination.
Pseudovirus neutralisation assay: A laboratory test using replication-deficient viral particles bearing the SARS-CoV-2 spike protein to measure neutralising antibody activity under biosafety-reduced conditions.
Immunobridging: A regulatory approach that infers vaccine efficacy in new populations or against novel variants by comparing immune responses to those elicited by vaccines with established efficacy.
References
- Predicting vaccine effectiveness against severe COVID-19 over time and against variants: a meta-analysis. Nature Communications (2023).
- Immune correlates analysis of the PREVENT-19 COVID-19 vaccine efficacy clinical trial. Nature Communications (2023).
- Antibody responses and correlates of protection in the general population after two doses of the ChAdOx1 or BNT162b2 vaccines. Nature Medicine (2022).
- Comparing antibody assays as correlates of protection against COVID-19 in the COVE mRNA-1273 vaccine efficacy trial. Science Translational Medicine (2023).
- Correlates of protection and determinants of SARS-CoV-2 breakthrough infections 1 year after third dose vaccination. BMC Medicine (2024).
- Neutralising antibody titres as predictors of protection against SARS-CoV-2 variants and the impact of boosting: a meta-analysis. The Lancet Microbe (2021).
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