Combined assessment of S‐ and N‐specific IL‐2 and IL‐13 secretion and CD69 neo‐expression for discrimination of post–infection and post‐vaccination cellular SARS‐CoV‐2‐specific immune response

Abstract

Background Antibody‐based tests are available for measuring SARS‐CoV‐2‐specific immune responses but fast T‐cell assays remain scarce. Robust T cell‐based tests are needed to differentiate specific cellular immune responses after infection from those after vaccination. Methods One hundred seventeen individuals (COVID‐19 convalescent patients: n = 40; SARS‐CoV‐2 vaccinees: n = 41; healthy controls: n = 36) were evaluated for SARS‐CoV‐2‐specific cellular immune responses (proliferation, Th1, Th2, Th17, and inflammatory cytokines, activation‐induced marker [AIM] expression) by incubating purified peripheral blood mononuclear cells (PBMC) or whole blood (WB) with SARS‐CoV‐2 peptides (S, N, or M), vaccine antigens (tetanus toxoid, tick borne encephalitis virus) or polyclonal stimuli ( Staphylococcal enterotoxin, phytohemagglutinin). Results N‐peptide mix stimulation of WB identified the combination of IL‐2 and IL‐13 secretion as superior to IFN‐γ secretion to discriminate between COVID‐19‐convalescent patients and healthy controls ( p < .0001). Comparable results were obtained with M‐ or S‐peptides, the latter almost comparably recalled IL‐2, IFN‐γ, and IL‐13 responses in WB of vaccinees. Analysis 10 months as opposed to 10 weeks after COVID‐19, but not allergic disease status, positively correlated with IL‐13 recall responses. WB cytokine responses correlated with cytokine and proliferation responses of PBMC. Antigen‐induced neo‐expression of the C‐type lectin CD69 on CD4 + ( p < .0001) and CD8 + ( p = .0002) T cells informed best about the SARS‐CoV‐2 exposure status with additional benefit coming from CD25 upregulation. Conclusion Along with N‐ and S‐peptide‐induced IL‐2 and CD69 neo‐expression, we suggest to include the type 2 cytokine IL‐13 as T‐cellular recall marker for SARS‐CoV‐2 specific T‐cellular immune responses after infection and vaccination.

IL‐13 determines specific IgE responses and SARS‐CoV‐2 immunity after mild COVID‐19 and novel mRNA vaccination

“…3B right). In line with a reported role for IL‐13 as a specific recall marker [ 27 ], these findings affirm the expression of IL‐13 as a characteristic feature of SARS‐CoV‐2 spike mRNA vaccination. Of note, the MODERNA mRNA vaccinated individuals showed higher IL‐13 levels (p = 0.033) compared to those donors vaccinated with BioNTech/Pfizer mRNA vaccine; however, there were no differences in anti‐HDM or IL‐33 levels between these subgroups (data not shown).…”

“…3F ). This particular role of IL‐13 is supported by its recently described function in SARS‐CoV‐2 specific recall responses after infection and vaccination [ 27 ]. As IL‐13 is associated with fast viral clearance [ 29 ] and patients with asthma driven by IL‐13 have a lower risk of death by COVID‐19 [ 30 ], the presence of a persistent concentration of IL‐13 in vaccinated or convalescent individuals may confer an advantage in the case of exposure to SARS‐CoV‐2, e.g.…”

Plant-Derived Extracellular Vesicles as a Delivery Platform for RNA-Based Vaccine: Feasibility Study of an Oral and Intranasal SARS-CoV-2 Vaccine

“…We observed an increase in CD69+ expression on both total CD3+ and CD3+CD4+ and CD3+CD8+. This finding was supported by previous studies that reported the induction of CD8+CD69+ [ 55 ] and CD4+CD69+ [ 56 ] following vaccination against SARS-CoV-2 [ 57 ]. Here, oEV-S1 treatment via the oral and IN routes induced a significant reduction in CD3+, CD3+CD4+, and CD3+CD8+ co-expressing CD25+, a typical marker of regulatory T cell (T reg).…”

Immunogenicity and In Vivo Protective Effects of Recombinant Nucleocapsid-Based SARS-CoV-2 Vaccine Convacell®

“…It induced a robust, early rising (i.e., already 14 days after the first injection) and long-lasting N-specific antibody response. Convacell ® stimulated an N-specific CD4 + and CD8 + T cell response which was characterized by a mixed Th1/Th2 cytokine profile in mice and in NSG mice engrafted with human PBMCs similar to that observed after natural SARS-CoV-2 infection [66]. Importantly, vaccination with Convacell ® protected Syrian hamsters against infection with SARS-CoV-2 as demonstrated by reduced weight loss, lowered virus RNA and ameliorated lung pathology as compared to non-immunized animals.…”