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

Abstract

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.

Keywords: COVID-19; SARS-CoV-2; effector T cell; intradermal; memory T cell; vaccine.

Figure 1

CONSORT chart of the study population. Healthy volunteers ages 18–60 years who had been vaccinated with two doses of inactivated SARS-CoV-2 vaccine for 8–12 weeks were randomized to receive different doses of the BNT162b2 mRNA vaccine (PZ). Thirty participants received a full dose (n = 30, PZ Group 1) or a half dose of the mRNA vaccine intramuscularly (IM) (n = 30, PZ Group 2). The last group received one-fifth of the dose intradermally (ID) (n = 31, PZ Group 3). The ChAdOx1 nCoV-19 vaccine (AZ) was also administered as a booster dose. After completion of a 4–8-week inactivated SARS-CoV-2 vaccination regimen, the participants were randomized to receive a full IM dose of the viral vector vaccine (n = 30, AZ Group 1) or a one-fifth ID dose of AZ (n = 30, AZ Group 2). An interval of >8–12 weeks was also included in the study. Additionally, the participants consented to receive an IM half dose of AZ (n = 30, AZ Group 3) or a one-fifth ID dose of AZ (n = 34, AZ Group 4). Fifteen samples from each group were selected for T cell analysis.

Figure 2

Effector cytokine responses induced by BNT162b2 mRNA vaccine booster administration. (A) Gating strategies for selecting CD4⁺ and CD8⁺ T cell populations. (B) Percentage of CD4⁺ and (D) CD8⁺ T cells. (C) Effector cytokine responses (IFN-γ⁺, TNF-α⁺ and IFN-γ⁺TNF-α⁺) of CD4⁺ and (E) CD8⁺ T cells. The p-value represents the median with a 95% confidence interval (CI). Statistical significance was assessed based on the Kruskal-Wallis test, followed by Dunn’s multiple comparisons test conducted between the vaccinated groups. No significant differences were observed.

Figure 3

Effector memory T cell (T_EM) responses after BNT162b2 mRNA vaccine booster administration. (A) Gating strategies for selecting CD4⁺ and CD8⁺ T_EM populations (CD45RO⁺CCR7⁻). (B) The proportion of memory T cell phenotypes presented in pie charts. (C) Percentage of S1-specific CD4⁺ and (E) CD8⁺ memory T cell phenotypes. (D) Effector cytokine responses (IFN-γ⁺, TNF-α⁺, and IFN-γ⁺TNF-α⁺) of S1-specific CD4⁺ and (F) CD8⁺ T_EM cells. The p-value represents the median with a 95% CI. Statistical significance was assessed based on the Kruskal–Wallis test, followed by Dunn’s multiple comparison test between the vaccinated groups.

Figure 4

Effector memory T cell (T_EM) responses after ChAdOx1 nCoV-19 vaccine booster administration. (A) Gating strategies for selecting CD4⁺ and CD8⁺ T_EM populations (CD45RO⁺CCR7⁻). (B) Proportions of memory T cell phenotypes represented in pie charts.

Figure 5

Effector cytokine responses induced by ChAdOx1 nCoV-19 vaccine booster administration. (A) Percentage of CD4⁺ and (C) CD8⁺ T cells. (B) Effector cytokine responses (IFN-γ⁺, TNF-α⁺, and IFN-γ⁺TNF-α⁺) of CD4⁺ and (D) CD8⁺ T cells. (E) Percentage of CD4⁺ and (G) CD8⁺ effector memory T cells (T_EM). (F) Effector cytokine responses (IFN-γ⁺, TNF-α⁺, and IFN-γ⁺TNF-α⁺) of CD4⁺ and (H) CD8⁺ T_EM. The p-value represents the median with a 95% CI. Statistical significance was assessed based on the Kruskal–Wallis test, followed by Dunn’s multiple comparisons test conducted between the vaccinated groups.