COVID-19 vaccines may elicit cross-reactive T-cell responses for long-term protection
01 Aug 2023
bởiSarah Cheung
Prof Chris Mok (left) and Prof David Hui (right)Researchers from the Chinese University of Hong Kong (CUHK) have reported that two doses of either mRNA-based BNT162b2 or inactivated CZ02 vaccine elicit cross-reactive T-cell responses. Identification of vaccine-induced memory T cells indicates potential long-term protection with COVID-19 vaccines.
“This is the first head-to-head comparative study on T-cell responses elicited by BNT162b2 or CZ02 in a community-based population,” said Professor David Hui of the Department of Medicine and Therapeutics, CUHK. “Our results support COVID-19 vaccination in the community, especially among individuals at high risk of severe complications.”
In the observational cohort study, the researchers isolated peripheral blood mononuclear cells (PBMCs) from 659 adults who received COVID-19 vaccines at three vaccination centres in Hong Kong between 21 May 2020 and 31 August 2021. Among these participants, 428 received two doses of either BNT162b2 or CZ02, 127 received two doses and a booster dose, 58 had a breakthrough Omicron infection after receiving two doses and a booster dose, and 46 had a non-Omicron infection before the first dose. [Lancet Microbe 2023:4;e418-e430]
T-cell responses were analyzed using PBMC samples stimulated by peptide pools of the spike protein or structural proteins (ie, spike, membrane, nucleocapsid, and envelope [S/M/N/E]) of wild-type SARS-CoV-2 or the Omicron BA.1 strain. The primary outcome was proportion of CD4-positive and CD8-positive T cells against SARS-CoV-2 at 1 month after vaccination or breakthrough infection.
Results from analysis with the wild-type S/M/N/E peptide pool showed that after vaccination, CD4-positive and CD8-positive T cells significantly increased in participants who received two doses of either BNT162b2 (CD4-positive T cells, p=1 x 10-16; CD8-positive T cells, p=1.2 x 10-13) or CZ02 (CD4-positive T cells, p=1 x 10-16; CD8-positive T cells, p=0.0022). No significant differences in T-cell responses against wild-type SARS-CoV-2 and Omicron BA.1 were observed in the BNT162b2 or CZ02 group. Although the spike peptide pool showed no significant increase in proportion of CD8-positive T cells against wild-type SARS-CoV-2 in the CZ02 group, other results were similar in the spike and S/M/N/E peptide pools.
In stratification analysis with the S/M/N/E peptide pool of Omicron BA.1, adults aged ≥60 years who received BNT162b2 had higher proportions of CD4-positive T cells (median, 0.015 percent vs 0.006 percent; p=0.0070) and CD8-positive T cells (median, 0.007 percent vs 0.000 percent; p=0.035) vs CZ02 recipients. Among those aged <60 years, BNT162b2 recipients had a higher proportion of Omicron-specific CD4-positive T cells (median, 0.012 percent vs 0.010 percent; adjusted p=0.031) than CZ02 recipients.
“A booster dose of CZ02 [or BNT162b2] may enhance waning T-cell responses [after two doses of CZ02],” noted Professor Chris Mok of the Jockey Club School of Public Health and Primary Care, CUHK. In participants who received two doses of CZ02, a booster dose of BNT162b2 or CZ02 enhanced waning T-cell responses, but these responses did not exceed those at 1 month after the second dose.
Similar T-cell responses against wild-type SARS-CoV-2 and Omicron BA.1 were observed in participants infected with Omicron BA.2 after three doses of vaccines and those with non-Omicron infection before the first dose.
COVID-19 vaccination may provide long-term protection against severe disease. In the study, memory T cells were identified among participants who had received two or three doses of vaccines, and one dose of vaccine after non-Omicron infection.
“Memory T cells in tissue can reactivate during COVID-19 infection. Thus, T-cell responses against different [SARS-CoV-2] variants may be effective for a long time,” Hui explained. [Annu Rev Immunol 2004;22:745-763; Nat Commun 2021;12:3010]