Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Measuring Variant-Specific Neutralizing Antibody Profiles after Bivalent SARS-CoV-2 Vaccinations by a Multivariant Surrogate Virus Neutralization Microarray

Version 1 : Received: 14 November 2023 / Approved: 15 November 2023 / Online: 15 November 2023 (17:01:16 CET)

How to cite: Springer, D.N.; Höltl, E.; Prüger, K.; Puchhammer-Stöckl, E.; Aberle, J.H.; Stiasny, K.; Weseslindtner, L. Measuring Variant-Specific Neutralizing Antibody Profiles after Bivalent SARS-CoV-2 Vaccinations by a Multivariant Surrogate Virus Neutralization Microarray. Preprints 2023, 2023111035. https://doi.org/10.20944/preprints202311.1035.v1 Springer, D.N.; Höltl, E.; Prüger, K.; Puchhammer-Stöckl, E.; Aberle, J.H.; Stiasny, K.; Weseslindtner, L. Measuring Variant-Specific Neutralizing Antibody Profiles after Bivalent SARS-CoV-2 Vaccinations by a Multivariant Surrogate Virus Neutralization Microarray. Preprints 2023, 2023111035. https://doi.org/10.20944/preprints202311.1035.v1

Abstract

The capability of antibodies to neutralize different SARS-CoV-2 variants varies among individuals depending on the previous exposure to wild-type- or Omicron-specific immunogens by mono- or bivalent vaccinations or infections. Such profiles of neutralizing antibodies (nAbs) usually have to be assessed by laborious live virus-neutralization tests (NTs). We therefore analyzed whether a novel multivariant surrogate virus neutralization test (sVNT) (adapted from a commercial microarray) that quantifies the antibody-mediated inhibition between the receptor angiotensin-converting-enzyme 2 (ACE2) and variant-specific receptor-binding domains (RBDs) can assess the neutralizing activity against SARS-CoV-2 wild-type, Delta Omicron BA.1, BA.2 and BA.5 (sub-) variants after a booster with Omicron-adapted bivalent vaccines in a manner similar to live-virus NTs. Indeed, by using the live-virus NTs as a reference, we found a significant correlation between the variant-specific NT titers and levels of ACE2-RBD binding inhibition (p < 0.0001, r ≤ 0.78 respectively). Furthermore, the sVNTs identified higher inhibition values against BA.5 and BA.1 in individuals vaccinated with Omicron-adapted vaccines than in those with monovalent wild-type vaccines. Our data thus demonstrate the ability of sVNTs to detect variant-specific nAbs following a booster with bivalent vaccines.

Keywords

SARS-CoV-2; Omicron; bivalent vaccination; neutralization;  assay; surrogate

Subject

Medicine and Pharmacology, Epidemiology and Infectious Diseases

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