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

Area of Science:

• Immunology
• Virology
• Vaccinology

Background:

• Immune memory is shaped by initial antigen exposure (priming).
• The SARS-CoV-2 pandemic allowed tracking of immune memory development after infection and vaccination.
• Hybrid immunity, from combined infection and vaccination, offers enhanced protection against SARS-CoV-2.

Purpose of the Study:

• To investigate how prior SARS-CoV-2 infection influences vaccine-induced immune memory.
• To compare immune responses in previously infected versus naive individuals after vaccination.

Main Methods:

• Analysis of SARS-CoV-2 RBD-specific memory B cells and neutralizing antibodies post-vaccination.
• Characterization of SARS-CoV-2 spike-specific CD4+ T cell cytokine profiles (IFN-γ, IL-10) in vaccinated individuals with different infection histories.

Main Results:

• Previously infected individuals generated more SARS-CoV-2 RBD-specific memory B cells and variant-neutralizing antibodies after vaccination.
• A distinct population of IFN-γ and IL-10-expressing memory SARS-CoV-2 spike-specific CD4+ T cells was observed in previously infected individuals.
• Additional vaccination in naive individuals boosted humoral memory but did not replicate the unique CD4+ T cell cytokine profile seen in hybrid immunity.

Conclusions:

• Imprinted features of SARS-CoV-2-specific memory lymphocytes are crucial for defining hybrid immunity.
• Prior infection significantly shapes the quality and characteristics of vaccine-induced immune memory, particularly T cell responses.