GLUT1 in Memory CD4+ T-cells Correlates with Sustained Antibody Responses and Polyfunctionality Post-RSV Vaccination in Immunocompromised Individuals 2250589

Abstract Introduction The immunogenicity of respiratory syncytial virus (RSV) vaccination in immunocompromised individuals is poorly understood due to limited published data in this population, specifically on cellular responses to novel RSV vaccines. To address this gap, T-cell responses were evaluated in immunocompromised individuals who received an approved RSV prefusion F (preF) protein subunit vaccine. Methods In a national prospective observational cohort, 44 immunocompromised individuals reported receiving either adjuvanted RSVPreF3 (AREXVY™) or unadjuvanted RSVpreF (ABRYSVO™). The cohort was predominantly solid organ transplant recipients but also included participants with autoimmune conditions on immunosuppressants. T-cell responses, RSV preF antibodies, and RSV neutralizing antibodies were assessed at baseline, early (2 or 4 weeks), and late (12 weeks) post-vaccination using flow cytometry following RSV-A2 fusion protein peptide pool stimulation, ELISA, and live-virus neutralization, respectively. Results Post-vaccination, there were significant increases in RSV-specific memory CD4+ T-cells producing IFN-γ, IL-2, and TNF, and increases in polyfunctional CD4+ T-cells. Both vaccines, without significant differences, increased CD4+ T-cell polyfunctionality. A subset of individuals did not have an increase in CD4+ T-cell responses, demonstrating the need to investigate predictors of response. GLUT1 (Glucose transporter 1) is a marker of T-cell metabolic activation and fitness. In cytokine-producing memory CD4+ T-cells, GLUT1 expression correlated with polyfunctionality, RSV F-specific IgG titers, and neutralizing antibody titers (NT50) at the late but not the early time point. Conclusion These findings suggest that sustained T-cell metabolic fitness, as indicated by GLUT1, may be linked to the durability of both cellular and humoral immune responses. Understanding the role of GLUT1 in shaping immune responses may provide novel methods for optimizing vaccine strategies for immunocompromised individuals. Funding Source National Institutes of Health (NIH) grants 1R01AI190359, 3U01AI138897-04S1, and 3UM1AI109565 Topic Categories Vaccines and Immunotherapy (VAC)