Employing T-Cell Memory to Effectively Target SARS-CoV-2

Abstract

Well-trained T-cell immunity is needed for early viral containment, especially with the help of an ideal vaccine. Although most severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected convalescent cases have recovered with the generation of virus-specific memory T cells, some cases have encountered T-cell abnormalities. The emergence of several mutant strains has even threatened the effectiveness of the T-cell immunity that was established with the first-generation vaccines. Currently, the development of next-generation vaccines involves trying several approaches to educate T-cell memory to trigger a broad and fast response that targets several viral proteins. As the shaping of T-cell immunity in its fast and efficient form becomes important, this review discusses several interesting vaccine approaches to effectively employ T-cell memory for efficient viral containment. In addition, some essential facts and future possible consequences of using current vaccines are also highlighted.

Keywords: COVID-19; SARS-CoV-2; T cells; lung TRM; vaccine.

Figure 1

A schematic diagram of vaccine strategy for an efficient T-cell immunity and its possible long-term consequences. (a) T cells should be primed with an ideal vaccine that includes several viral proteins such as structural and non-structural proteins to be able to broadly target SARS-CoV-2, a similar response which can be seen in convalescent COVID-19 cases. In the future, vaccine strategies should be improved by targeting specific immunodominant and immunogenic epitopes. (b) Nasal vaccine as a booster dose is a promising strategy to induce TRM cell response at the viral entry sites such as the respiratory tract and lungs in addition to the systemic T-cell immunity. (c) Convalescent cases may have TRM cells in the lungs, but the cell number will decrease over time. (d) The frequency of lung TRM levels in convalescent cases can be restored by using the nasal vaccine approach (b,d) Vaccination by nasal route is a promising strategy to recruit virus-specific T cells to the respiratory tract. A swift CD8⁺ TRM response by intranasal vaccine as a booster can effectively control the virus at the respiratory tracts and lungs. However, there are some potential negative consequences of the intranasal approach such as non-specific bystander activation of TRM cells, heterologous immunity to similar epitopes, and chronic inflammation with its long-term complications such as metaplasia and dysplasia.