AUTHOR=Chirkova Tatiana , Rosas-Salazar Christian , Gebretsadik Tebeb , Jadhao Samadhan J. , Chappell James D. , Peebles R. Stokes , Dupont William D. , Newcomb Dawn C. , Berdnikovs Sergejs , Gergen Peter J. , Hartert Tina V. , Anderson Larry J. TITLE=Effect of Infant RSV Infection on Memory T Cell Responses at Age 2-3 Years JOURNAL=Frontiers in Immunology VOLUME=Volume 13 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.826666 DOI=10.3389/fimmu.2022.826666 ISSN=1664-3224 ABSTRACT=Background: It is unknown whether RSV infection in infancy alters subsequent RSV immune responses. Methods: In a nested cohort of healthy, term children, peripheral blood mononuclear cells (PBMCs) were collected at ages 2-3 years to examine RSV memory T cell responses among children previously RSV infected during infancy (first year of life) compared to those RSV-uninfected during infancy. The presence vs. absence of infant RSV infection was determined through a combination of RSV molecular and serologic testing. Memory responses were measured in RSV stimulated PBMCs. Results: Compared to children not infected with RSV during the first year of life, children infected with RSV during infancy had lower memory T cell responses at ages 2-3 years to in vitro stimulation with RSV for most tested type-1 and type-17 markers for a number of memory T cell subsets. Conclusions: RSV infection in infancy has long-term effects on memory T cell responses. This is the first study to show the potential for RSV infection in infancy to have long-term effects on the immune memory irrespective of the severity of the infection. Our results suggest a possible mechanism through which infant RSV infection may result in greater risk of subsequent childhood respiratory viral morbidity, findings also relevant to vaccine development.