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Correlation of antibody titers with COVID-19 vaccine efficacy

Determining the efficacy of a vaccine in development can be achieved by a number of routes, including lengthy placebo-controlled trials. However, the urgency of the coronavirus disease 2019 (COVID-19) pandemic – caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogen – shifts focus towards developing fast and cost-effective efficacy correlation methods, one of which may be the quantification of antibody titers in sera.

Study: Evidence for antibody as a protective correlate for COVID-19 vaccines. Image Credit: Maria Kaminska / Shutterstock

In a paper recently uploaded to the preprint server medRxiv*, the relationship between virus-neutralizing antibody and spike protein-binding IgG antibody levels is explored following vaccination by one of seven currently deployed vaccines. The findings support the use of antibody titers as correlates of protection for COVID-19 vaccines.

How was the study performed?

Data regarding the efficacy of each of the Pfizer, Moderna, Gamaleya, AstraZeneca, Sinovac, Novavax, and Janssen vaccines was collected, in particular including datasets with serum SARS-CoV-2 neutralization or binding antibody titers, collected by enzyme-linked immunosorbent assay (ELISA) from patient plasma samples.

Virus neutralizing antibodies directly inactivate a virus by blocking cell entry, replication, or other vital function, while binding IgG antibodies tag pathogens for removal by macrophages or other immune cells. The titers of SARS-CoV-2 neutralizing antibody and SARS-CoV-2 spike-protein binding IgG antibodies, determined by ELISA assay of patient plasma, were compared against vaccine efficacy over a period of four weeks following the manufacturers recommended vaccination regimen.

Only a low correlation between efficacy and neutralizing antibody titers was initially observed, as has been reported in a large number of other studies that imply a low generation of these antibodies following vaccination. However, these assays were performed in a number of settings, in a range of laboratories from around the world, and recalibration of these assays revealed a good correlation between neutralizing and binding antibody titer levels and efficacy, 77.5% and 94.2%, respectively.

Unlike neutralizing antibody levels, spike-protein binding IgG antibody levels have been observed to rise following vaccine administration in many other vaccine studies, being well correlated. The group also advises that other factors in addition to antibody titers may impact virus efficacy, and thus correlation does not necessarily demonstrate causation.

In this short paper, the group argues that establishing a system that allows better comparison of antibody measurements, from numerous laboratories from around the world, using a standardized proficiency panel, would enable the efficacy of vaccines in early clinical trials to be determined more quickly than currently possible.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

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