1. Strong antigen-specific T-cell immunity induced by a recombinant human TERT measles virus vaccine and amplified by a DNA/viral vector prime boost in IFNAR/CD46 mice.
- Author
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Pliquet E, Ruffie C, Escande M, Thalmensi J, Najburg V, Combredet C, Bestetti T, Julithe M, Liard C, Huet T, Wain-Hobson S, Tangy F, and Langlade-Demoyen P
- Subjects
- Animals, CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes metabolism, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes metabolism, Cancer Vaccines genetics, Cell Line, Chlorocebus aethiops, Cytokines metabolism, Cytotoxicity, Immunologic, Humans, Immunization, Immunization, Secondary, Mice, Mice, Transgenic, Telomerase genetics, Vaccines, DNA, Vero Cells, Cancer Vaccines immunology, Epitopes, T-Lymphocyte immunology, Genetic Vectors genetics, Immunity, Cellular, Measles virus genetics, T-Lymphocytes immunology, Telomerase immunology
- Abstract
Cancer immunotherapy is seeing an increasing focus on vaccination with tumor-associated antigens (TAAs). Human telomerase (hTERT) is a TAA expressed by most tumors to overcome telomere shortening. Tolerance to hTERT can be easily broken both naturally and experimentally and hTERT DNA vaccine candidates have been introduced in clinical trials. DNA prime/boost strategies have been widely developed to immunize efficiently against infectious diseases. We explored the use of a recombinant measles virus (MV) hTERT vector to boost DNA priming as recombinant live attenuated measles virus has an impressive safety and efficacy record. Here, we show that a MV-TERT vector can rapidly and strongly boost DNA hTERT priming in MV susceptible IFNAR/CD46 mouse models. The cellular immune responses were Th1 polarized. No humoral responses were elicited. The 4 kb hTERT transgene did not impact MV replication or induction of cell-mediated responses. These findings validate the MV-TERT vector to boost cell-mediated responses following DNA priming in humans.
- Published
- 2019
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