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Title: Repetitive peptide boosting progressively enhances functional memory CTLs

Author
item SMYTH, KENDRA - University Of Maryland
item GARCIA, KARLA - University Of Maryland
item SUN, ZHIFENG - University Of Maryland
item Tuo, Wenbin
item XIAO, ZHENGGUO - University Of Maryland

Submitted to: Biochemical and Biophysical Research Communications
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/15/2012
Publication Date: 8/3/2012
Citation: Smyth, K., Garcia, K., Sun, Z., Tuo, W., Xiao, Z. 2012. Repetitive peptide boosting progressively enhances functional memory CTLs. Biochemical and Biophysical Research Communications. 424(3):635-640.

Interpretive Summary: Functional T cells are key to vaccination, however, induction of these T cells during vaccination is very challenging. In the present study, we show that large number of functional T cells can be induced by repeated intravenous administration of the same vaccine formulation. The resulting T cells are able to provide protection against experimental infection. In addition, our immunization procedure drives the differentiation of these T cells to a unique phenotype, characterized by decreased interferon-gamma but increased granzyme B production. Furthermore, different adjuvants appear to have similar effects on the enhancement of the T cells. The T cells induced by our procedure can respond to infection by vigorous growth. These data demonstrate that repeated intravenous immunization is an effective approach to enhance functional T cell response in vaccination. These results will benefit the scientific community by providing basic information on immune regulation and vaccine research and development.

Technical Abstract: Induction of functional memory CTLs holds promise for fighting critical infectious diseases through vaccination, but so far, no effective regime has been identified. We show here that memory CTLs can be enhanced progressively to high levels by repetitive intravenous boosting with peptide and adjuvant. The resulting memory CTLs are functional and able to provide protection against pathogen challenge. In addition, repetitive boosting drives the differentiation of memory CTLs to a unique and long-lasting effector memory phenotype characterized by decreased interferon-gamma but increased granzyme B production. Furthermore, enhancement of functional memory CTLs can be similarly achieved by using different adjuvants. Lastly, memory CTLs from multiple rounds of boosting strongly respond to pathogen insults, and thus are not immune senescent. These data demonstrate that repeated intravenous peptide boosting with adjuvant is an effective approach to enhance functional memory CTLs in vaccination.