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- Title
Distinct receptor binding domain IgG thresholds predict protective host immunity across SARS-CoV-2 variants and time.
- Authors
Kenny, Grace; O'Reilly, Sophie; Wrigley Kelly, Neil; Negi, Riya; Gaillard, Colette; Alalwan, Dana; Saini, Gurvin; Alrawahneh, Tamara; Francois, Nathan; Angeliadis, Matthew; Garcia Leon, Alejandro Abner; Tinago, Willard; Feeney, Eoin R.; Cotter, Aoife G.; de Barra, Eoghan; Yousif, Obada; Horgan, Mary; Doran, Peter; Stemler, Jannik; Koehler, Philipp
- Abstract
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. Evidence from trials suggests SARS-CoV-2 binding antibody thresholds could serve as surrogate markers of neutralising capacity, but whether this is accurate in the context of variants of concerns, or in the event of prior infection or vaccination remains unclear. Authors explore the performance of receptor binding domain IgG thresholds in predicting a level of neutralising capacity that has demonstrated protection against infection in vaccine trials
- Subjects
SARS-CoV-2; BOOSTER vaccines; VACCINE trials; IMMUNITY; BIOMARKERS; IMMUNOGLOBULINS
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-42717-1