title: Vaccine efficacy and T helper cell differentiation change with aging.
abstract: Influenza and pneumonia are leading causes of death in elderly populations. With age, there is an increased inflammatory response and slower viral clearance during influenza infection which increases the risk of extended illness and mortality. Here we employ a preclinical murine model of influenza infection to examine the protective capacity of vaccination with influenza nucleoprotein (NP). While NP vaccination reduces influenza-induced lung inflammation in young mice, aged mice do not show this reduction, but are protected from influenza-induced mortality. Aged mice do make a significant amount of NP-specific IgG and adoptive transfer experiments show that NP antibody can protect from death but cannot reduce lung inflammation. Furthermore, young but not aged vaccinated mice generate significant numbers of NP-specific T cells following subsequent infection and few of these T cells are found in aged lungs early during infection. Importantly, aged CD4 T cells have a propensity to differentiate towards a T follicular helper (Tfh) phenotype rather than a T helper 1 (Th1) phenotype that predominates in the young. Since Th1 cells are important in viral clearance, reduced Th1 differentiation in the aged is critical and could account for some or all of the age-related differences in vaccine responses and infection resolution.
authors.affiliation: The Trudeau Institute, Saranac Lake, NY, United States of America.|Département de Pneumologie, Centre de Recherche de l'Institut Universitaire de Cardiologie et Pneumologie de Québec, Québec, QC, Canada.
authors.forename: Julie S
authors.initials: JS
authors.lastname: Lefebvre
authors.affiliation: Department of Immunology and Center on Aging, University of Connecticut Health Center, Farmington, CT, United States of America.
authors.forename: Erica C
authors.initials: EC
authors.lastname: Lorenzo
authors.affiliation: Department of Immunology and Center on Aging, University of Connecticut Health Center, Farmington, CT, United States of America.
authors.forename: April R
authors.initials: AR
authors.lastname: Masters
authors.affiliation: Department of Immunology and Center on Aging, University of Connecticut Health Center, Farmington, CT, United States of America.
authors.forename: Jacob W
authors.initials: JW
authors.lastname: Hopkins
authors.affiliation: The Trudeau Institute, Saranac Lake, NY, United States of America.
authors.forename: Sheri M
authors.initials: SM
authors.lastname: Eaton
authors.affiliation: The Trudeau Institute, Saranac Lake, NY, United States of America.|NIAID/NIH, Bethesda, MD, USA.
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Smiley
authors.affiliation: Department of Immunology and Center on Aging, University of Connecticut Health Center, Farmington, CT, United States of America.
authors.forename: Laura
authors.initials: L
authors.lastname: Haynes
mesh_terms: D000375:Aging / Q000276:immunology*; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D019590:Nucleocapsid Proteins; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D016601:RNA-Binding Proteins / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014758:Viral Core Proteins / Q000276:immunology
chemical_list: D007252:Influenza Vaccines; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins
keywords: Gerotarget; Th subsets; aging; antibody; influenza; influenza vaccination