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

Abstract

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. While 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.

Abstract

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.