Regulatory T Cells Decreased during Recovery from Mild COVID-19

Depending on the intensity and duration of SARS-CoV-2 infection, the host immune response plays a significant role in immunological protection. Here, we studied the regulatory T-cell (Treg) response in relation to kinetic change and cytokine production in patients with mild COVID-19. Nineteen SARS-CoV-2-positive patients were recruited, and blood was collected at four time points, i.e., seven days after admission, after discharge, and one and three months after recovery. CD3+CD4+CD25+CD127low was marked as the Treg population, with IL-10 and TGF-β used to study cytokine-producing Tregs. IFN-γ-producing CD8+ T cells were observed for an effector response. The Treg percentage in patients with mild COVID-19 increased during hospitalization compared to during the recovery period. Peripheral blood mononuclear cells (PBMCs) were quantified, and the T-cell response was characterized by re-stimulation with S1 and N peptides. IL-10 and TGF-β were produced by CD25+CD127low T cells during the active infection phase, especially with N peptide stimulation. Compared to N peptide stimulation, S1 peptide stimulation provided superior IFN-γ-secreting CD8+ T-cell responses. Our results suggest that while IFN-γ+CD8+ T cells confer antiviral immunity, cytokine-producing Tregs may have a substantial role in regulating inflammatory responses in mild SARS-CoV-2 infection. Novel vaccine development may also consider enhancing T-cell repertoires

Heterologous COVID-19 Vaccination and Booster with mRNA Vaccine Provide Enhanced Immune Response in Patients with Cirrhosis: A Prospective Observational Study

This study aimed to evaluate the antibody and cellular responses to different coronavirus 2019 (COVID-19) vaccination regimens in patients with cirrhosis and to assess the antibody response after a vaccine booster. We conducted a prospective observational study of 89 patients with cirrhosis and 41 healthy volunteers who received two COVID-19 vaccine doses. Next, we prospectively evaluated 24 patients with cirrhosis who received a booster COVID-19 vaccine dose. In both studies, blood samples were collected before and 4 weeks after vaccination, and anti-spike receptor-binding domain protein IgG levels, T-cell phenotypes, and effector functions were assessed. The heterologous vaccine regimen (CoronaVac [SV]/AstraZeneca [AZ]) produced a better antibody response and CD4+IFNg+ T cell response compared to homogeneous vaccine regimens. The antibody response after the second dose of the vaccine was similar in patients with cirrhosis and healthy volunteers. Patients who received a booster dose of the mRNA vaccine had significantly increased antibody titers compared to those who received the AZ vaccine. In patients with cirrhosis, heterologous vaccination with SV/AZ resulted in a better immune response than the AZ/AZ and SV/SV regimens. Moreover, a booster dose of the mRNA vaccine led to a greater increase in antibody titers compared to the AZ vaccine

T-Cell Responses Induced by an Intradermal BNT162b2 mRNA Vaccine Booster Following Primary Vaccination with Inactivated SARS-CoV-2 Vaccine

A practical booster vaccine is urgently needed to control the coronavirus disease (COVID-19) pandemic. We have previously reported the safety and immunogenicity of a fractional intradermal booster, using the BNT162b2 mRNA vaccine in healthy volunteers who had completed two doses of inactivated SARS-CoV-2 vaccine. In this study, an intramuscular booster at full dosage was used as a control, and a half-dose vaccination was included for reciprocal comparison. Detailed T-cell studies are essential to understand cellular responses to vaccination. T-cell immunity was examined using S1 peptide restimulation and flow cytometry. The fractional dose (1:5) of the BNT162b2 mRNA vaccine enhanced antigen-specific effector T-cells, but the responses were less remarkable compared to the intramuscular booster at full dosage. However, the intradermal regimen was not inferior to the intramuscular booster a month after boosting. An intradermal booster using only one-fifth of the standard dosage could provide comparable T-cell responses with the fractional intramuscular booster. This work confirms the efficacy of intradermal and fractional vaccination in terms of T-cell immunogenicity in previously immunised populations

Intradermal Fractional ChAdOx1 nCoV-19 Booster Vaccine Induces Memory T Cells: A Follow-Up Study

The administration of viral vector and mRNA vaccine booster effectively induces humoral and cellular immune responses. Effector T cell responses after fractional intradermal (ID) vaccination are comparable to those after intramuscular (IM) boosters. Here, we quantified T cell responses after booster vaccination. ChAdOx1 nCoV-19 vaccination induced higher numbers of S1-specific CD8+ memory T cells, consistent with the antibody responses. Effector memory T cell phenotypes elicited by mRNA vaccination showed a similar trend to those elicited by the viral vector vaccine booster. Three months post-vaccination, cytokine responses remained detectable, confirming effector T cell responses induced by both vaccines. The ID fractional dose of ChAdOx1 nCoV-19 elicited higher effector CD8+ T cell responses than IM vaccination. This study confirmed that an ID dose-reduction vaccination strategy effectively stimulates effector memory T cell responses. ID injection could be an improved approach for effective vaccination programs