Garin-Ortega, L. | Search bioRxiv

bioRxiv2026

Durability and diversity of human upper airway T cell memory

T cells are major contributors to protective immunity against pathogens and cancers. Immune memory is a central feature of protective adaptive immunity, and mucosal barrier tissues are major sites of pathogen invasion. Yet, fundamental gaps remain in our knowledge of human T cell immune memory durability in mucosal barrier sites. Here, we employed minimally invasive nasal swab sampling to directly detect, and longitudinally assess, human antigen-specific T cells in two upper airway tissue sites (~ 900 samples) and peripheral blood. Antigen-specific memory CD8 and CD4 T cells were detected in upper airway tissue of > 95% of individuals. Both memory CD8 and CD4 T cells were sustained in both mucosal epithelial and mucosal lymphoid tissue over the course of 18+ months, with monthly sampling, and no clear evidence of decline. Virus-specific upper airway CD8 and CD4 T cells were predominantly resident memory T cells (TRM) throughout the 18+ month period of observation. These findings can inform future T cell vaccines and therapeutics.

immunology↗

bioRxiv2025

Local B-cell immunity and durable memory following live-attenuated influenza intranasal vaccination of humans

Seasonal influenza vaccines are most frequently delivered as intramuscular inactivated vaccines which elicit systemic responses against the immunodominant hemagglutinin (HA) head domain. An intranasally administered, live-attenuated influenza vaccine designed to stimulate mucosal immunity, FluMist, is the sole intranasal vaccine approved in the United States. However, FluMist has lower systemic immunogenicity and efficacy in adults compared to intramuscular formulations. In this study, human mucosal and systemic immunity were examined following seasonal intramuscular or intranasal vaccination. Nasopharyngeal swabs of adenoid tissue were used to longitudinally sample the upper airway. Notably, FluMist induced substantial increases in upper respiratory tract IgG+ and IgA+ HA-specific memory B cells, which displayed an activated CD27+CD21- phenotype. H1, H3, and influenza B virus HA-specific memory B cells were all detected in the upper airway after intranasal immunization and remained elevated at 6-months post-vaccination. Recently activated upper airway memory B cells were not readily detected in intramuscular vaccinees, despite marked elevation of systemic antibody and memory B cells. Thus, despite minimal immune response detected in circulation, live-attenuated influenza vaccine can generate substantial local antigen-specific memory B cell responses in adults. These findings have implications for improving influenza vaccines and for mucosal vaccination against other respiratory pathogens. One Sentence SummaryLongitudinal nasopharyngeal sampling reveals local influenza-specific B cell responses following intranasal but not intramuscular vaccination.

immunology↗