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Lookup NU author(s): Jess Tyerman, Dr Christopher DuncanORCiD, Dr Rebecca PayneORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Pronounced immune escape by the SARS-CoV-2 Omicron variant has resulted inmany individuals possessing hybrid immunity, generated through a combination ofvaccination and infection. Concerns have been raised that omicron breakthroughinfections in triple-vaccinated individuals result in poor induction of omicron-specific immunity, and that prior SARS-CoV-2 infection is associated with immune dampening.Taking a broad and comprehensive approach, we characterize mucosal and bloodimmunity to spike and non-spike antigens following BA.1/BA.2 infections in triplemRNA-vaccinated individuals, with and without prior SARS-CoV-2 infection. We findthat most individuals increase BA.1/BA.2/BA.5-specific neutralising antibodiesfollowing infection, but confirm that the magnitude of increase and post-omicron titresare higher in the infection-naive. In contrast, significant increases in nasal responses, including neutralizing activity against BA.5 spike, are seen regardless of infection history. Spike-specific T cells increase only in infection-naive vaccinees; however,post-omicron T cell responses are significantly higher in the previously-infected, whodisplay a maximally induced response with a highly cytotoxic CD8+ phenotypefollowing their 3rd mRNA vaccine dose. Responses to non-spike antigens increasesignificantly regardless of prior infection status. These findings suggest that hybridimmunity induced by omicron breakthrough infections is characterized by significantimmune enhancement that can help protect against future omicron variants.
Author(s): Hornsby H, Nicols A, Longet S, Liu C, Tomic A, Angyal A, Kronsteiner B, Tyerman J, Tipton T, Zhang P, Gallis M, Supasa P, Selvaraj M, Abraham P, Neale I, Ali M, Barratt N, Nell J, Gustafsson L, Strickland S, Grouneva I, Rostron T, Moore S, Hering L, Dobson S, Bibi S, Mongkolsapaya J, Lambe T, Wootton D, Hall V, Hopkins S, Dong T, Barnes E, Screaton G, Richter A, Turtle L, Rowland-Jones S, Carroll M, Duncan CJA, Klenerman P, Dunachie S, Payne R, de Silva T
Publication type: Article
Publication status: Published
Journal: Nature Communications
Year: 2023
Volume: 14
Online publication date: 21/08/2023
Acceptance date: 02/08/2023
Date deposited: 05/08/2023
ISSN (electronic): 2041-1723
Publisher: Nature Publishing Group
URL: https://doi.org/10.1038/s41467-023-40592-4
DOI: 10.1038/s41467-023-40592-4
Data Access Statement: The full dataset used in this study has been made available at the Open Science Framework, https://doi.org/10.17605/OSF.IO/9TSZ645. The FCS data used in the UMAP and marker expression analysis have been deposited in the Zenodo databases https://doi.org/10.5281/zenodo.8045040 and https://doi.org/10.5281/zenodo.804510746,47. Source data are provided with this paper. Code availability The code used to undertake the UMAP and marker expression analysis in Figs. S4–6 has been deposited in the Zenodo databases https://doi.org/10.5281/zenodo.8045040 and https://doi.org/10.5281/zenodo.8045107
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