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

Abstract

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.

Keywords: COVID-19; T-cells; inactivated SARS-CoV-2; intradermal; mRNA vaccine.

Figure 1

Effector cytokine production of S1-specific CD4⁺ T-cells after BNT162b2 boosting. All volunteers were previously vaccinated with two doses of inactivated SARS-CoV-2 vaccines (n = 91). The BNT162b2 mRNA booster was administered in three groups: full dose intramuscularly (n = 30), half dose intramuscularly (n = 30), and one-fifth vaccine dose intradermally (n = 31). (a) CD4⁺ and CD8⁺ T-cell populations, (b) percentage of CD4⁺ T-cells at Day 0 (before booster dose), Day 14, and Day 28 (after booster dose), (c) S1-specific IFN-γ-producing CD4⁺ T-cells, (d) percentage of S1-specific IFN-γ-producing CD4⁺ T-cell responses at Day 0 (before booster dose), Day 14, and Day 28 (after booster dose), (e) S1-specific TNF-α-producing CD4⁺ T-cells, (f) Percentage of S1-specific TNF-α producing CD4⁺ T-cell responses at Day 0 (before booster dose), Day 14, and Day 28 (after booster dose). Each symbol represents the median of one participant with 95% CI (n = 30–31 volunteers). Statistical significance was determined using the Kruskal–Wallis’s test, with Dunn’s multiple comparison test between vaccinated groups. * p ≤ 0.05; ** p ≤ 0.01.

Figure 2

Effector cytokine production of S1-specific CD8⁺ T-cells after BNT162b2 boosting. All volunteers were previously vaccinated with two doses of inactivated SARS-CoV-2 vaccines (n = 91). The BNT162b2 mRNA booster vaccine was administered in three groups: intramuscularly with either full dosage (n = 30), or half dosage (n = 30), and intradermally with fractional dosage (n = 31). (a) CD4⁺ T-cell and CD8⁺ T-cell populations, (b) percentage of CD8⁺ T-cells at Day 0 (before booster dose), Day 14 and Day 28 (after booster dose), (c) S1-specific IFN-γ-producing CD8⁺ T-cells, (d) percentage of S1-specific IFN-γ-producing CD8⁺ T-cell responses at Day 0 (before booster dose), Day 14, and Day 28 (after booster dose), (e) S1-specific TNF-α-producing CD8⁺ T-cells, (f) percentage of S1-specific TNF-α-producing CD8⁺ T-cell responses at Day 0 (before booster dose), Day 14, and Day 28 (after booster dose). Each symbol represents the median of one participant with 95% CI (n = 30–31 volunteers). Statistical significance was determined using the Kruskal–Wallis’s test, with Dunn’s multiple comparison test between vaccinated groups. * p ≤ 0.05.