Distinct receptor binding domain IgG thresholds predict protective host immunity across SARS-CoV-2 variants and time

Grace Kenny, Sophie O’Reilly, Neil Wrigley Kelly, Riya Negi, Colette Gaillard, Dana Alalwan, Gurvin Saini, Tamara Alrawahneh, Nathan Francois, Matthew Angeliadis, Alejandro Abner Garcia Leon, Willard Tinago, Eoin R. Feeney, Aoife G. Cotter, Eoghan de Barra, Obada Yousif, Mary Horgan, Peter Doran, Jannik Stemler, Philipp KoehlerRebecca Jane Cox, Donal O’Shea, Ole F. Olesen, Alan Landay, Andrew E. Hogan, Jean Daniel Lelievre, Virginie Gautier, Oliver A. Cornely, Patrick W.G. Mallon, Alejandro Garcia Leon, Eoin Feeney, Eoghan de Barra

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


SARS-CoV-2 neutralising antibodies provide protection against COVID-19. Evidence from early vaccine trials suggested binding antibody thresholds could serve as surrogate markers of neutralising capacity, but whether these thresholds predict sufficient neutralising capacity against variants of concern (VOCs), and whether this is impacted by vaccine or infection history remains unclear. Here we analyse individuals recovered from, vaccinated or with hybrid immunity against SARS-CoV-2. An NT50 ≥ 100 IU confers protection in vaccine trials, however, as VOC induce a reduction in NT50, we use NT50 ≥ 1000 IU as a cut off for WT NT50 that would retain neutralisation against VOC. In unvaccinated convalescent participants, a receptor binding domain (RBD) IgG of 456 BAU/mL predicts an NT50 against WT of 1000 IU with an accuracy of 80% (95%CI 73–86%). This threshold maintains accuracy in determining loss of protective immunity against VOC in two vaccinated cohorts. It predicts an NT50 < 100 IU against Beta with an accuracy of 80% (95%CI 67–89%) in 2 vaccine dose recipients. In booster vaccine recipients with a history of COVID-19 (hybrid immunity), accuracy is 87% (95%CI 77–94%) in determining an NT50 of <100 IU against BA.5. This analysis provides a discrete threshold that could be used in future clinical studies.

Original languageEnglish (US)
Article number7015
JournalNature communications
Issue number1
StatePublished - Dec 2023
Externally publishedYes

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy


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