Historically, vaccines have been approved based on a single measurement of antibody titers, but such measurements fail to capture the complexity of the protective immune response. Our recent work demonstrates protective immunity against pathogens is mediated by the integrated action of the innate and T and B cell responses in tissues. For example, we recently showed that tissue resident memory T cells (TRMs) can lower the threshold of neutralizing antibody required for protection against mucosal infection, by stimulating heightened local innate responses in tissues ¹. Similarly, we observe that intravenous vaccination with the tuberculosis vaccine BCG results in a sustained antigen-specific CD4+ T cell response that feeds back on lung myeloid and epithelial cells to imprint prolonged antiviral innate resistance against a broad array of viruses including influenza, SARS-CoV-2 and its variants and related coronaviruses². We are currently using exploring the molecular mechanisms underlying this “integrated organ immunity” against pathogens³.