ABSTRACT
Resident memory T cells (TRM) 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 (Ag)-specific TRM are detectable beyond 11 months in the lung of convalescent COVID-19 patients after mild and severe infection1, it is unknown if mRNA vaccination encoding for the SARS-CoV-2 S-protein can induce this frontline protection. We found that the frequency of CD4+ T cells secreting interferon (IFN)g in response to S-peptides was similar in the lung of mRNA-vaccinated patients compared to convalescent-infected patients. However, in vaccinated patients, lung responses presented less frequently a TRM phenotype compared to convalescent infected individuals and polyfunctional TRM were virtually absent. Thus, a robust and wide TRM response established in convalescent-infected individuals may be advantageous in limiting disease if the virus is not block by initial mechanisms of protection, such as neutralization. Still, mRNA vaccines can induce modest responses within the lung parenchyma potentially contributing to the overall disease control.