Rebecca Slotkin, Tassos C. Kyriakides, Anupam Kundu, Gary Stack, Richard E. Sutton, Shaili Gupta
Abstract
The objective of this study was to describe the correlation between the commercially available assay for anti-S1/RBD IgG and protective serum neutralizing antibodies (nAb) against SARS-CoV-2 in an adult population after SARS-CoV-2 vaccination, and determine if clinical variables impact this correlation.
Introduction
High levels of anti-SARS-CoV-2 neutralizing antibodies (nAb) have been shown to correlate with protection against severe infection with SARS-CoV-2 [1]. Messenger RNA (mRNA) vaccines elicit the production of nAb, but the ability to reliably detect nAb is limited to research laboratory settings. The FDA is in the process of deciding the optimal vaccination schedule for SARS-CoV-2 with a goal of simplifying the vaccination regimen [2]. Neither the CDC nor FDA currently recommend using commercially available antibody testing to assess post-vaccination immunity or to determine the timing of booster doses [3,4]. However, using commercially available assays that reliably predict nAb levels in clinical settings could allow for rapid and customizable decisions for patients regarding the optimal SARS-CoV-2 vaccination schedule and timing of booster doses.
Materials and method
Approval for this study (SARS-CoV-2 Vaccine and You, Protocol #1599488) was obtained from the Veterans Affairs Connecticut Healthcare System (VACHS) Institutional Review Board (IRB) in December 2020. Written informed consent was obtained from willing participants recruited from COVID-vaccination clinics set up by VACHS beginning in December 2020. Participants were eligible if they were either veterans or healthcare workers working at VACHS. Participants were excluded if they had an illness or condition that prohibited their informed consent.
Results
We obtained 127 sera samples from 100 unique subjects (Table 1). Log10IgG values demonstrated a strong correlation with log10IC50 values (R2 = 0.83, Radj = 0.70, p < 0.0001) (Fig 1), and significantly predicted log10 IC50 values (beta = 0.56, p = 0) on univariable analysis. We found that a IgG of > 25,000 predicted a robust IC50 of > 400 in all participants.
Discussion
Our results demonstrate a robust correlation between IgG anti-SARS-CoV-2 S1/RBD and anti-SARS-CoV-2 neutralization antibodies, suggesting that IgG anti-S1/RBD could be used to predict neutralizing antibody immune response. These findings may open avenues for further use of commercially available antibody testing in lower-resourced research settings, where rapid diagnostic testing is generally preferred [10]. Antibody testing will not provide a guarantee against infection, but could help guide clinical decisions, such as the timing and frequency of re-vaccination with a goal of preventing severe infections. Antibody testing is already being used sporadically in primary care settings, although guidelines and evidence for this use are limited [11,12]. Further research into appropriate cut-off values which indicate immune protection, and the impact of host factors will be important to refine and better guide rapid antibody testing in clinical settings.
Conclusions
There is a robust correlation between sera IgG anti-S1/RBD and neutralizing antibody IC50 titers, which is impacted by certain clinical variables such as prior COVID infection and renal function. Further understanding of the clinical factors that impact this correlation will be important for ongoing clinical or research applications of commercial antibody platforms. Commercially available antibody testing, such as the CMIA assay described in this study, can play an important role in lowering the cost and infrastructure barriers to assessing the levels of clinically active neutralizing antibodies. An understanding of neutralizing antibody titers may enable more nuanced patient conversations about SARS-CoV-2 immunity and frequency of vaccine booster doses, although further research will be needed to guide this use. We should leverage the tools we have available to refine rapid diagnostic antibody testing, lower barriers to SARS-CoV-2 research, and add clinical relevance to the optimal frequency of SARS-CoV-2 re-vaccination, especially in the presence of certain clinical factors.
Acknowledgments
We thank our laboratory staff who worked on our pseudotyping and commercial assay, as well as our subjects for donating their samples.
Citation: Slotkin R, Kyriakides TC, Kundu A, Stack G, Sutton RE, Gupta S (2023) Correlation of a commercial platform’s results with post-vaccination SARS-CoV-2 neutralizing antibody response and clinical host factors. PLoS ONE 18(8): e0289713. https://doi.org/10.1371/journal.pone.0289713
Editor: Harapan Harapan, Universitas Syiah Kuala, INDONESIA
Received: March 30, 2023; Accepted: July 25, 2023; Published: August 29, 2023
This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Data Availability: De-identified individual participant-level data that underlie the results reported in this paper are shared in S1 File.
Funding: Funding for this study was provided by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (R01 AI150334 to RES). The analysis was supported by Global Health Equity Scholars through the Fogarty International Center of the National Institutes of Health and the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (FIC D43TW010540 and T32AR007107 to RS). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0289713#ack
