Limited induction of polyfunctional lung-resident memory T cells against SARS-CoV-2 by mRNA vaccination compared to infection

Resident memory T cells (T RM ) present at the respiratory tract may be essential to enhance early SARS-CoV-2 viral clearance, thus limiting viral infection and disease. While long-term antigen-specific T RM are detectable beyond 11 months in the lung of convalescent COVID-19 patients, it is unknown if mRNA vaccination encoding for the SARS-CoV-2 S-protein can induce this frontline protection. Here we show that the frequency of CD4 + T cells secreting IFNγ in response to S-peptides is variable but overall similar in the lung of mRNA-vaccinated patients compared to convalescent-infected patients. However, in vaccinated patients, lung responses present less frequently a T RM phenotype compared to convalescent infected individuals and polyfunctional CD107a + IFNγ + T RM are virtually absent in vaccinated patients. These data indicate that mRNA vaccination induces specific T cell responses to SARS-CoV-2 in the lung parenchyma, although to a limited extend. It remains to be determined whether these vaccine-induced responses contribute to overall COVID-19 control. Resident memory T cells at the respiratory tract may play critical roles in the response to respiratory infections including SARS-CoV-2. Here the authors characterise the lung resident T cell response generated in response to mRNA vaccination of SARS-CoV-2 Spike or in convalescent patients after natural infection. They show reduced frequency and functionality of tissue resident T cells in vaccinated versus convalescent patients which may impact disease control and vaccination strategies.