Type I IFN Induced by Adenovirus Serotypes 28 and 35 Has Multiple Effects on T Cell Immunogenicity

作者: Matthew J. Johnson , Constantinos Petrovas , Takuya Yamamoto , Ross W. B. Lindsay , Karin Loré

DOI: 10.4049/JIMMUNOL.1103717

关键词: CellRecombinant DNAVirologyT cellCytotoxic T cellBiologyTropismVector (molecular biology)AdenoviridaeMolecular biologyImmunogenicity

摘要: Recombinant adenovirus (rAd) vectors are being investigated as vaccine delivery vehicles in preclinical and clinical studies. rAds constructed from different serotypes differ receptor usage, tropism, ability to activate cells, aspects of which likely contribute their immunogenicity profiles. In this study, we compared the infectivity cell stimulatory capacity recombinant serotype 5 (rAd5), 28 (rAd28), 35 (rAd35) association with respective We found that rAd28 rAd35 infected led vitro maturation activation both human mouse dendritic cells more efficiently rAd5. stark contrast rAd5, induced production IFN-α stimulated IFN-related intracellular pathways. However, vivo was significantly lower than Deletion signaling during vaccination increased magnitude insert-specific T response levels by rAd5 vector. The negative impact on could be overcome increasing dose, also associated greater polyfunctionality a favorable long-term memory phenotype CD8 presence signaling. Taken together, our results demonstrate rAd-induced has multiple effects immunogenicity, understanding should considered design rAd vectors.

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