title: Age-related changes in durability and function of vaccine-elicited influenza-specific CD4(+) T-cell responses.
abstract: The major antigenic component of licensed influenza vaccines, hemagglutinin (HA), elicits predominantly type-specific antibody responses, thus necessitating frequent antigenic updates to the annual vaccine. However, accumulating evidence suggests that influenza vaccines can also induce significant cross-reactive T-cell responses to highly divergent, heterosubtypic HA antigens not included in the vaccine. Influenza vaccines are less effective among the elderly and studies that characterize cross-reactive T-cell immunity in this vulnerable population are much needed. Here, we systematically compare the ex vivo frequency, cytokine profile and phenotype of vaccine-elicited HA-specific T-cell responses among a cohort of young (18-49 years old) and elderly (≥70 years old) vaccinees, as well as the maturation and activation phenotype of total CD4(+) and CD8(+) T-cells. IFN-γ production after in vitro expansion and HA-specific Ab titers were also determined. We find that vaccine-elicited ex vivo frequencies of CD4(+) T-cells elicited by vaccination reactive to any given homo- or heterosubtypic Ag were comparable across the two age groups. While, no differences were observed between age groups in the phenotype of Ag-specific or total CD4(+) T-cells, PBMC from young adults were superior at producing IFN-γ after short-term Ag-specific culture. Significantly, while vaccine-elicited T-cell responses were durable among the younger vaccinees, they were short-lived among the elderly. These results have important ramifications for our understanding of vaccine-induced changes in the magnitude and functionality of HA-specific CD4(+) T-cells, as well as age-related alterations in response kinetics.
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Yolanda D
authors.initials: YD
authors.lastname: Mahnke
authors.forename: Areej
authors.initials: A
authors.lastname: Saqr
authors.forename: Staci
authors.initials: S
authors.lastname: Hazenfeld
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Brady
authors.forename: Mario
authors.initials: M
authors.lastname: Roederer
authors.forename: Ramu A
authors.initials: RA
authors.lastname: Subbramanian
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D006801:Humans; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D007371:Interferon-gamma