Kinetics and ability of binding antibody and surrogate virus neutralization tests to predict neutralizing antibodies against the SARS-CoV-2 Omicron variant following BNT162b2 booster administration

Clin Chem Lab Med. 2023 Apr 21;61(10):1875-1885. doi: 10.1515/cclm-2022-1258. Print 2023 Sep 26.

Abstract

Objectives: To assess the long-term humoral immunity induced by booster administration, as well as the ability of binding antibody and surrogate virus neutralization tests (sVNT) to predict neutralizing antibodies (NAbs) against the SARS-CoV-2 Omicron variant.

Methods: A total of 269 sera samples were analyzed from 64 healthcare workers who had received a homologous booster dose of BNT162b2. Neutralizing antibodies assessed by sVNT and anti-RBD IgG measured with the sCOVG assay (Siemens Healthineers®) were analyzed at five timepoints; before and up to 6 months following the booster. Antibody titers were correlated with neutralizing antibodies against the Omicron BA.1 variant obtained by pseudovirus neutralization test (pVNT) as a reference method.

Results: While Wild-type sVNT percentage of inhibition (POI) remained above 98.6% throughout the follow-up period after booster administration, anti-RBD IgG and NAbs assessed by Omicron BA.1 pVNT showed respectively a 3.4-fold and 13.3-fold decrease after 6 months compared to the peak reached at day 14. NAbs assessed by Omicron sVNT followed a steady decline until reaching a POI of 53.4%. Anti-RBD IgG and Omicron sVNT assays were strongly correlated (r=0.90) and performed similarly to predict the presence of neutralizing antibodies with Omicron pVNT (area under the ROC: 0.82 for both assays). In addition, new adapted cut-off values of anti-RBD IgG (>1,276 BAU/mL) and Omicron sVNT (POI>46.6%) were found to be better predictors of neutralizing activity.

Conclusions: This study showed a significant drop in humoral immunity 6 months after booster administration. Anti-RBD IgG and Omicron sVNT assays were highly correlated and could predict neutralizing activity with moderate performance.

Keywords: BNT162b2 mRNA vaccine; Omicron; SARS-CoV-2; binding antibodies; neutralizing antibodies; surrogate virus neutralization tests.

MeSH terms

  • Antibodies, Neutralizing*
  • Antibodies, Viral
  • BNT162 Vaccine
  • COVID-19*
  • Humans
  • Immunoglobulin G
  • Kinetics
  • Neutralization Tests
  • SARS-CoV-2

Substances

  • Antibodies, Neutralizing
  • BNT162 Vaccine
  • Immunoglobulin G
  • Antibodies, Viral

Supplementary concepts

  • SARS-CoV-2 variants