Highly immunostimulatory RNA derived from a Sendai virus defective viral genome
详细信息 查看全文
- 作者：Xiomara Mercado-L贸pez ; Christopher R. Cotter ; Won-keun Kim ; Yan Sun ; Luis Mu帽oz ; Karla Tapia ; Carolina B. L贸pez
- 关键词：DVG ; defective virus genome ; DPs ; defective particles ; IFN ; interferon ; MDA5 ; melanoma differentiation-associated protein 5 ; poly I ; C ; polyinosinic ; polycytidylic acid ; RIG-I ; retinoic acid-inducible gene 1 ; RLRs ; RIG-I-like receptors ; RSV ; respiratory syncytial virus ; inRSV ; formalin-inactivated RSV ; SeV ; Sendai virus ; SeV HD ; SeV high content of defective particles ; SeV LD ; SeV depleted of defective particles
- 刊名：Vaccine
- 出版年：19 November, 2013
- 年：2013
- 卷：31
- 期：48
- 页码：5713-5721
- 全文大小：2141 K
文摘
Defective viral genomes (DVGs) are generated during virus replication. DVGs bearing complementary ends are strong inducers of dendritic cell (DC) maturation and of the expression of antiviral and pro-inflammatory cytokines by triggering signaling of the RIG-I family of intracellular pattern recognition receptors. Our data show that DCs stimulated with virus containing DVGs have an enhanced ability to activate human T cells and can induce adaptive immunity in mice. In addition, we describe the generation of a short Sendai virus (SeV)-derived DVG RNA (DVG-324) that maintains strong immunostimulatory activity in vitro and in vivo. DVG-324 induced high levels of Ifnb expression when transfected into cells and triggered fast expression of pro-inflammatory cytokines and mobilization of dendritic cells when injected into the footpad of mice. Importantly, DVG-324 enhanced the production of antibodies to a prototypic vaccine after a single intramuscular immunization in mice. Notably, the pro-inflammatory cytokine profile induced by DVG-324 was different from that induced by poly I:C, the only viral RNA analog currently used as an immunostimulant in vivo, suggesting a distinct mechanism of action. SeV-derived oligonucleotides represent novel alternatives to be harnessed as potent adjuvants for vaccination.