SARS-CoV-2 breakthrough infection in vaccinees induces virus-specific nasal-resident CD8+ and CD4+ T cells of broad specificity

Rapid recognition of SARS-CoV-2-infected cells by resident T cells in the upper airway might provide an important layer of protection against COVID-19. Whether parenteral SARS-CoV-2 vaccination or infection induces nasal-resident T cells specific for distinct SARS-CoV-2 proteins is unknown. We isolated T cells from the nasal mucosa of COVID-19 vaccinees who either experienced SARS-CoV-2 infection after vaccination (n = 34) or not (n = 16) and analyzed their phenotype, SARS-CoV-2 specificity, function, and persistence. Nasal-resident SARS-CoV-2-specific CD8(+) and CD4(+) T cells were detected almost exclusively in vaccinees who experienced SARS-CoV-2 breakthrough infection. Importantly, the Spike-specific T cells primed by vaccination did not suppress the induction of T cells specific for other SARS-CoV-2 proteins. The nasal-resident T cell responses persisted for >= 140 d, with minimal sign of waning. These data highlight the importance of viral nasal challenge in the formation of SARS-CoV-2-specific antiviral immunity at the site of primary infection and further define the immunological features of SARS-CoV-2 hybrid immunity. Virus-specific T cells in the nasal cavity might provide an immediate layer of protection against SARS-CoV-2. This study detected SARS-CoV-2-specific nasal-resident T cells in vaccinees only after infection, highlighting the significance of nasal challenge in the formation of antiviral immunity at the site of infection.

Automated summary

Nasal-resident T cells specific for SARS-CoV-2 were detected in vaccinated individuals only after infection, highlighting the significance of nasal challenge in the formation of antiviral immunity at the site of infection.