Omicron Neutralizing and Anti-SARS-CoV-2 S-RBD Antibodies in Naïve and Convalescent Populations After Homologous and Heterologous Boosting With an mRNA Vaccine

Abstract

Background: The omicron variant has spread globally at unprecedented speed due to a combination of epidemiological and virological factors that still need to be fully unraveled. Although boosting of immunity in vaccinated populations has proven to increase the antibody recognition for this variant, we still ignore the impact that this intervention has on protection from infection and disease.

Methods: Relying on a live virus neutralization assay and a commercial chemiluminescence immunoassay targeting antibodies against the receptor binding domain (RBD) of the parental Spike protein, we tested the efficacy of homologous and heterologous booster vaccinations in inducing antibodies against SARS-CoV-2 parental, delta, beta and omicron variants by history of SARS-CoV-2 infection and age of population. Booster vaccination was performed with the BNT126b2 vaccine, while individuals who underwent heterologous booster vaccination were primed with the ChAdOx1 nCov-19 vaccine. Moreover, we studied the impact that prior immunity has on vaccination, in mildly infected individuals who received 2-3 doses of the BNT1262b vaccine at different times after infection. Children previously infected with delta were evaluated 3·5 months after infection. To translate neutralization data into estimates of protection, we relied on published predictive models and inferred variant-specific thresholds of protection for both assays and assessed the accuracy of the commercial assay at identifying highly protected individuals.

Findings: We confirm that boosting significantly restores the ability of antibodies to recognize omicron and other variants, and that the homologous protocol with the BNT126b2 vaccine achieves higher and more broadly reactive neutralizing antibody titers, than those observed among individuals who crossed-over vaccines. On the other hand, mild prior infection with the parental virus and subsequent homologous vaccination with BNT126b2 induces high antibody levels, but with moderate breadth of response, while children aged 5-11 show negligible neutralizing antibodies against the omicron variant few months from infection. Neutralizing and binding antibodies correlate across all variants and allow the identification of variant-specific anti-RBD thresholds for 90% protection efficacy.

Interpretation: Boosting with the BNT126b2 vaccine is an immediate and effective measure to increase the protection against omicron, in naïve, as well as in previously infected individuals. Identification through serological commercial assays of thresholds of protection against the omicron and delta variants is a crucial step towards large-scale serosurveys to finely assess infection risk both at population and individual level. 

Funding Information: This publication was supported by the ORCHESTRA and VERDI projects and has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreements No. 101016167 and No. 101045989.

Declaration of Interests: The authors have no conflict of interest.

Ethics Approval Statement: The studies were conducted in accordance with the Declaration of Helsinki, and authorized by the Institutional Review Boards of the University of Padova (study 1, protocol number 7862; study 3 protocol number 70714) and the University of Verona (protocol number 884 and 3199) and Istituto Nazionale Lazzaro Spallanzani, Rome, Italy (protocol number 436). All subjects older than 18 years and the legally authorized representatives of minors were informed of the research proposals and provided written consent for the collection and use of biological specimens and routine patient-based data for research purposes.

Keywords: omicron, correlate, neutralization, chemiluminescence, SARS-CoV-2