A Severe Acute Respiratory Syndrome Coronavirus 2 Anti-Spike Immunoglobulin G Assay: A Robust Method for Evaluation of Vaccine Immunogenicity Using an Established Correlate of Protection

Abstract

As the COVID-19 pandemic continues, variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge. Immunogenicity evaluation of vaccines and identification of correlates of protection for vaccine effectiveness is critical to aid the development of vaccines against emerging variants. Anti-recombinant spike (rS) protein immunoglobulin G (IgG) quantitation in the systemic circulation (serum/plasma) is shown to correlate with vaccine efficacy. Thus, an enzyme-linked immunosorbent assay (ELISA)-based binding assay to detect SARS-CoV-2 (ancestral and variant strains) anti-rS IgG in human serum samples was developed and validated. This assay successfully met acceptance criteria for inter/intra-assay precision, specificity, selectivity, linearity, lower/upper limits of quantitation, matrix effects, and assay robustness. The analyte in serum was stable for up to 8 freeze/thaw cycles and 2 years in −80 °C storage. Similar results were observed for the Beta, Delta, and Omicron BA.1/BA.5/XBB.1.5 variant-adapted assays. Anti-rS IgG assay results correlated significantly with neutralization and receptor binding inhibition assays. In addition, usage of international reference standards allows data extrapolation to WHO international units (BAU/mL), facilitating comparison of results with other IgG assays. This anti-rS IgG assay is a robust, high-throughput method to evaluate binding IgG responses to S protein in serum, enabling rapid development of effective vaccines against emerging COVID-19 variants.

Multivalent and Sequential Heterologous Spike Protein Vaccinations Effectively Induce Protective Humoral Immunity against SARS-CoV-2 Variants

“…Receptor hACE2 binding inhibition levels were observed to be correlated with virus neutralization titers in mice [13]. Previous studies reported a correlation between IgG titers of spike antigen binding and receptor hACE2 binding inhibition, as well as between hACE2 binding inhibition and neutralizing antibody titers in human blood samples [26][27][28]. This study in a mouse model suggests that a strategy of multivalent COVID-19 vaccination might be applicable for inducing effective immunity.…”

A Pseudovirus-Based Neutralization Assay for SARS-CoV-2 Variants: A Rapid, Cost-Effective, BSL-2–Based High-Throughput Assay Useful for Vaccine Immunogenicity Evaluation

“…For correlation with anti-S IgG antibodies and hACE2 binding inhibition, the samples were tested using a validated anti-S IgG assay (Clinical Immunology, Novavax) and using a previously published method [ 15 ] or a validated hACE2 binding inhibition assay (Clinical Immunology, Novavax) [ 16 ], followed by comparison of the data with the PNT results using linear regression analysis.…”

Immunogenicity and Safety of Heterologous Omicron BA.1 and Bivalent SARS-CoV-2 Recombinant Spike Protein Booster Vaccines: A Phase 3 Randomized Clinical Trial

“…For the analysis of difference of SRRs, based on an assumption of 80% SRR for NVX-CoV2373 and 85% SRR for NVX-CoV2515, there was 90% power to conclude noninferiority with a margin of −5% (NVX-CoV2515 relative to NVX-CoV2373). Participant serum antibody concentrations were measured via a previously validated assay [ 18 ].…”