Impaired SARS-CoV-2-Specific CD8+ T Cells After Infection or Vaccination but Robust Hybrid T Cell Immunity in Patients with Multiple Myeloma.

Background: Multiple myeloma (MM) patients are at high risk of severe infections including COVID-19 due to an immune dysregulation affecting both innate and adaptive immune responses. However, our understanding of the immune responses to infection and vaccination in MM patients is limited. To gain more detailed insights into infection- and vaccine-elicited T cell immunity in MM, we studied the CD8+ T cell response on the single-epitope level in SARS-CoV-2 convalescent and mRNA-vaccinated MM patients.

Rapid and stable mobilization of CD8 T cells by SARS-CoV-2 mRNA vaccine.

SARS-CoV-2 spike mRNA vaccines mediate protection from severe disease as early as ten days after prime vaccination, when neutralizing antibodies are hardly detectable. Vaccine-induced CD8 T cells may therefore be the main mediators of protection at this early stage. The details of their induction, comparison to natural infection, and association with other arms of vaccine-induced immunity remain, however, incompletely understood.

Memory-like HCV-specific CD8 T cells retain a molecular scar after cure of chronic HCV infection.

In chronic hepatitis C virus (HCV) infection, exhausted HCV-specific CD8 T cells comprise memory-like and terminally exhausted subsets. However, little is known about the molecular profile and fate of these two subsets after the elimination of chronic antigen stimulation by direct-acting antiviral (DAA) therapy. Here, we report a progenitor-progeny relationship between memory-like and terminally exhausted HCV-specific CD8 T cells via an intermediate subset.

Characterization of pre-existing and induced SARS-CoV-2-specific CD8 T cells.

Emerging data indicate that SARS-CoV-2-specific CD8 T cells targeting different viral proteins are detectable in up to 70% of convalescent individuals. However, very little information is currently available about the abundance, phenotype, functional capacity and fate of pre-existing and induced SARS-CoV-2-specific CD8 T cell responses during the natural course of SARS-CoV-2 infection. Here, we define a set of optimal and dominant SARS-CoV-2-specific CD8 T cell epitopes.