title: Efficacy of a vaccine that links viral epitopes to flagellin in protecting aged mice from influenza viral infection.
abstract: Influenza vaccines are less effective in older people than younger people. This impaired ability to protect older people from influenza viral lung infection has important implications as older people suffer a higher morbidity and mortality from influenza viral lung infection than younger people. Therefore, the development of novel effective vaccines that induce protection from influenza viral infections in older people are urgently needed. We had previously shown that direct linking the TLR5 activator, flagellin, to viral peptides induces effective immunity to viral antigens in young mice and people, respectively. In this study, we tested the efficacy of this vaccine platform with the hemagglutinin peptide of the influenza A strain virus (vaccine denoted as STF2.HA1-2) in protecting aged mice from subsequent influenza viral lung infection. We found that a 3.0 μg dose of the vaccine was effective in reducing mortality and increasing clinical well-being during influenza viral lung infection in aged mice. However, this effect was inferior to the response induced in young mice. Defects in the adaptive immune system but not the innate immune system were associated with this reduced effectiveness of the vaccine with aging. Our results indicate that the STF2.HA1-2 vaccine is effective in protecting aged hosts from influenza lung infection, although defects in the adaptive immune system with aging may limit the effectiveness of this vaccine in older people.
authors.affiliation: Department of Internal Medicine and Immunobiology, Yale University of Medicine, New Haven, CT, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Leng
authors.forename: Heather W
authors.initials: HW
authors.lastname: Stout-Delgado
authors.forename: Uma
authors.initials: U
authors.lastname: Kavita
authors.forename: Andrea
authors.initials: A
authors.lastname: Jacobs
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.forename: Wei
authors.initials: W
authors.lastname: Du
authors.forename: Lynda
authors.initials: L
authors.lastname: Tussey
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Goldstein
mesh_terms: D000375:Aging / Q000276:immunology; D000818:Animals; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D005408:Flagellin / Q000235:genetics / Q000276:immunology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D016019:Survival Analysis; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000939:Epitopes; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D014614:Vaccines, Synthetic; D005408:Flagellin