The impact of pre-existing cross-reactive immunity on SARS-CoV-2 infection and vaccine responses

• Published in: Nature reviews. Immunology Vol. 23; no. 5; pp. 304 - 316
• Main Authors: Murray, Sam M., Ansari, Azim M., Frater, John, Klenerman, Paul, Dunachie, Susanna, Barnes, Eleanor, Ogbe, Ane
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2023; Nature Publishing Group
• Subjects: 631/250/2152/1566/1571; 692/420/2780; Biomedical and Life Sciences; Biomedicine; Common cold; Coronaviridae; Coronaviruses; COVID-19; COVID-19 - prevention & control; COVID-19 Vaccines; Cross-reactivity; Epitopes; Homology; Humans; Immune response; Immune response (cell-mediated); Immune response (humoral); Immunology; Infections; Lymphocytes T; Perspective; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Vaccination; Vaccine development; Vaccines
• ISSN: 1474-1733; 1474-1741; 1474-1741
• DOI: 10.1038/s41577-022-00809-x

Pre-existing cross-reactive immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins in infection-naive subjects have been described by several studies. In particular, regions of high homology between SARS-CoV-2 and common cold coronaviruses have been highlighted as a likely source of this cross-reactivity. However, the role of such cross-reactive responses in the outcome of SARS-CoV-2 infection and vaccination is currently unclear. Here, we review evidence regarding the impact of pre-existing humoral and T cell immune responses to outcomes of SARS-CoV-2 infection and vaccination. Furthermore, we discuss the importance of conserved coronavirus epitopes for the rational design of pan-coronavirus vaccines and consider cross-reactivity of immune responses to ancestral SARS-CoV-2 and SARS-CoV-2 variants, as well as their impact on COVID-19 vaccination. This Review discusses the evidence for pre-existing cross-reactive immune responses to SARS-CoV-2, which are mainly due to infections with common cold coronaviruses, and how such cross-reactivity affects adaptive immune responses. Furthermore, it explores cross-reactivity in the context of SARS-CoV-2 variants of concern and its implications for vaccine development.