Age-related changes in durability and function of vaccine-elicited influenza-specific CD4(+) T-cell responses

作者：Mahnke Yolanda D; Saqr Areej; Hazenfeld Staci; Brady Rebecca C; Roederer Mario; Subbramanian Ramu A^*

来源：Vaccine, 2011, 29(47): 8606-8614.

DOI：10.1016/j.vaccine.2011.09.019

• Hemagglutinin
• Durability
• T-cell quality
• Proliferation

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-gamma 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-gamma 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.

• 出版日期2011-11-3