Repetitive peptide boosting progressively enhances functional memory CTLs

• Published in: Biochemical and biophysical research communications Vol. 424; no. 3; pp. 635 - 640
• Main Authors: Smyth, Kendra, Garcia, Karla, Sun, Zhifeng, Tuo, Wenbin, Xiao, Zhengguo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03.08.2012
• Subjects: Adjuvant; Adjuvants, Immunologic - administration & dosage; Adoptive Transfer; Animals; Boosting; Cytotoxicity; Immunization, Secondary - methods; Immunologic Memory; Memory; Mice; Mice, Inbred Strains; Peptide; Peptides - administration & dosage; Peptides - immunology; T cells; T-Lymphocytes, Cytotoxic - immunology; Cytotoxicity; Boosting; Adjuvant; T cells; Peptide; Memory
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2012.07.018

► Intravenous peptide boosting with adjuvant can induce large numbers of functional memory CTLs. ► Repetitively boosted CTLs are long-lasting and stable in effector memory phenotype. ► CTLs possess a unique phenotype of down-regulated IFNγ and up-regulated granzyme B production. ► These results are observed in both transgenic and endogenous models. Cytotoxic T lymphocytes (CTLs) play a critical role in controlling intracellular pathogens and cancer cells, and induction of memory CTLs holds promise for developing effective vaccines against critical virus infections. However, generating memory CTLs remains a major challenge for conventional vector-based, prime-boost vaccinations. Thus, it is imperative that we explore nonconventional alternatives, such as boosting without vectors. We show here that repetitive intravenous boosting with peptide and adjuvant generates memory CD8 T cells of sufficient quality and quantity to protect against infection in mice. The resulting memory CTLs possess a unique and long-lasting effector memory phenotype, characterized by decreased interferon-γ but increased granzyme B production. These results are observed in both transgenic and endogenous models. Overall, our findings have important implications for future vaccine development, as they suggest that intravenous peptide boosting with adjuvant following priming can induce long-term functional memory CTLs.