Imprinted SARS-CoV-2-specific memory lymphocytes define hybrid immunity

• Published in: Cell Vol. 185; no. 9; pp. 1588 - 1601.e14
• Main Authors: Rodda, Lauren B., Morawski, Peter A., Pruner, Kurt B., Fahning, Mitchell L., Howard, Christian A., Franko, Nicholas, Logue, Jennifer, Eggenberger, Julie, Stokes, Caleb, Golez, Inah, Hale, Malika, Gale, Michael, Chu, Helen Y., Campbell, Daniel J., Pepper, Marion
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28.04.2022
• Subjects: adaptive immune response; Antibodies, Neutralizing; Antibodies, Viral; antigens; COVID-19; COVID-19 - immunology; COVID-19 Vaccines - immunology; cytokines; human; Humans; hybrid Immunity; Immunity, Humoral; immunologic memory; memory; memory B cell; memory T cell; pandemic; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus; T-Lymphocytes; vaccination; vaccine; COVID-19; SARS-CoV-2; vaccine; memory T cell; memory B cell; hybrid Immunity; adaptive immune response; human
• ISSN: 0092-8674; 1097-4172; 1097-4172
• DOI: 10.1016/j.cell.2022.03.018

Immune memory is tailored by cues that lymphocytes perceive during priming. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic created a situation in which nascent memory could be tracked through additional antigen exposures. Both SARS-CoV-2 infection and vaccination induce multifaceted, functional immune memory, but together, they engender improved protection from disease, termed hybrid immunity. We therefore investigated how vaccine-induced memory is shaped by previous infection. We found that following vaccination, previously infected individuals generated more SARS-CoV-2 RBD-specific memory B cells and variant-neutralizing antibodies and a distinct population of IFN-γ and IL-10-expressing memory SARS-CoV-2 spike-specific CD4+ T cells than previously naive individuals. Although additional vaccination could increase humoral memory in previously naive individuals, it did not recapitulate the distinct CD4+ T cell cytokine profile observed in previously infected subjects. Thus, imprinted features of SARS-CoV-2-specific memory lymphocytes define hybrid immunity. [Display omitted] •Vaccination elicits robust SARS-CoV-2-specific immune memory regardless of prior infection•Hybrid immunity is associated with more virus-specific memory B cells and Omicron nAb•SARS-CoV-2 infection prior to vaccination elicits a robust CD4+ T Th1/IFN-ɣ response•Infection-induced Th1/IFN-ɣ signature is not reproduced by three vaccinations The strong immunity against SARS-CoV-2 in vaccinated individuals that have previously been infected can be explained by a combination of RBD-specific memory B cells, variant-neutralizing antibodies, and a specific population of CD4+ T cells.