title: A push-pull vaccine strategy using Toll-like receptor ligands, IL-15, and blockade of negative regulation to improve the quality and quantity of T cell immune responses.
abstract: We have developed a strategy to optimize the efficacy of vaccines to induce T-cell immunity against chronic viral infections and cancer based on a "push-pull" approach in which we first optimize the antigen structure by increasing the affinity of epitopes for major histocompatibility complex molecules ("epitope enhancement"), then push the response not only in magnitude but also in quality toward the desired response phenotype, using synergistic combinations of cytokines, Toll-like receptor ligands, and costimulatory molecules, and then pull the response by removing the brakes exerted by negative regulatory mechanisms, including regulatory cells, cell surface molecules, and cytokines. Components of this approach show promise in macaque models of AIDS virus infection and in murine models of cancer, and are being developed for human clinical trials.
authors: Vaccine Branch, Center for Cancer Research, National Cancer Institute, Building 10, Room 6B-04 (MSC#1578) NIH, Bethesda, MD 20892-1578, USA. berzofsk@helix.nih.gov
authors: Jay A
authors: JA
authors: Berzofsky
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D007111:Immunity, Cellular; D019409:Interleukin-15 / Q000276:immunology*; D008024:Ligands; D051193:Toll-Like Receptors / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D000939:Epitopes; D019409:Interleukin-15; D008024:Ligands; D051193:Toll-Like Receptors; D014765:Viral Vaccines