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

重组人 TERT 麻疹病毒疫苗在 IFNAR/CD46 小鼠中诱导并通过 DNA/病毒载体初次增强扩增的强抗原特异性 T 细胞免疫力

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作者:Elodie Pliquet, Claude Ruffie, Marie Escande, Jessie Thalmensi, Valérie Najburg, Chantal Combredet, Thomas Bestetti, Marion Julithe, Christelle Liard, Thierry Huet, Simon Wain-Hobson, Frédéric Tangy, Pierre Langlade-Demoyen

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.

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