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Vaccine. 2013 Nov 19;31(48):5713-21. doi: 10.1016/j.vaccine.2013.09.040. Epub 2013 Oct 5.

Highly immunostimulatory RNA derived from a Sendai virus defective viral genome.

Author information

1
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States.

Abstract

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.

KEYWORDS:

Adjuvant; DPs; DVG; Defective genomes; Dendritic cells; IFN; Immunization; MDA5; RIG-I; RIG-I-like receptors; RLRs; RSV; SeV; SeV HD; SeV LD; SeV depleted of defective particles; SeV high content of defective particles; Sendai virus; defective particles; defective virus genome; interferon; melanoma differentiation-associated protein 5; poly I:C; polyinosinic:polycytidylic acid; respiratory syncytial virus: inRSV, formalin-inactivated RSV; retinoic acid-inducible gene 1

PMID:
24099876
PMCID:
PMC4406099
DOI:
10.1016/j.vaccine.2013.09.040
[Indexed for MEDLINE]
Free PMC Article

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