Renaissance of antiviral CD8⁺ T cell immunity in vaccination and disease

Over the past 20 years, the limited efficacy of CD8⁺ T cell-based vaccines against viruses in clinical trials has shifted attention away from such strategies. However, recent findings have brought renewed appreciation for the central importance of CD8⁺ T cells in controlling both acute and chronic viral infections and in preventing severe or progressive disease. This work highlights shared features, such as effector functions and stemness properties, of effective CD8⁺ T cell responses against diverse viruses such as SARS-CoV-2 and HIV. A deeper understanding and simpler interpretation of the functional workings of CD8⁺ T cell-mediated immunity, combined with advances in immunological and biotechnological tools, are opening new avenues for eliciting optimal T cell responses, both for prophylactic and for therapeutic applications. Collectively, these developments revive optimism that vaccines and immunotherapies designed to harness robust CD8⁺ T cell responses could have a major role in combating emerging viral threats and in achieving long-term suppression of persistent infections such as HIV-1 to undetectable levels.