Immunoprophylactic strategies against respiratory influenza virus infection

Saravolac, Edward G.; Sabuda, D; Crist, Colin; Blasetti, Karen; Schnell, Glen; Yang, Huanming; Kende, Meir; Levy, Hilton B.; Wong, Jonathan P.

doi:10.1016/s0264-410x(00)00450-3

Cited by 15 publications

(9 citation statements)

References 22 publications

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“…Activation of innate immunity and production of cytokines such as type I interferon are known to inhibit viral infection. For example, polyI:C in complex with poly-l-lysine and methylcellulose (polyICLC), either alone or encapsulated in liposomes, protects mice from otherwise lethal Infl uenza A infection (Saravolac et al, 2001). In spite of the obvious interplay between immune stimulation and antiviral activity, at the time of writing, only one published study has compared chemically modifi ed to unmodifi ed (immunostimulatory) siRNA .…”

Section: Off-target Effectsmentioning

confidence: 99%

siRNA and Innate Immunity

2009

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Canonical small interfering RNA (siRNA) duplexes are potent activators of the mammalian innate immune system. The induction of innate immunity by siRNA is dependent on siRNA structure and sequence, method of delivery, and cell type. Synthetic siRNA in delivery vehicles that facilitate cellular uptake can induce high levels of inflammatory cytokines and interferons after systemic administration in mammals and in primary human blood cell cultures. This activation is predominantly mediated by immune cells, normally via a Toll-like receptor (TLR) pathway. The siRNA sequence dependency of these pathways varies with the type and location of the TLR involved. Alternatively nonimmune cell activation may also occur, typically resulting from siRNA interaction with cytoplasmic RNA sensors such as RIG1. As immune activation by siRNA-based drugs represents an undesirable side effect due to the considerable toxicities associated with excessive cytokine release in humans, understanding and abrogating this activity will be a critical component in the development of safe and effective therapeutics. This review describes the intracellular mechanisms of innate immune activation by siRNA, the design of appropriate sequences and chemical modification approaches, and suitable experimental methods for studying their effects, with a view toward reducing siRNA-mediated off-target effects.

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Section: Off-target Effectsmentioning

confidence: 99%

siRNA and Innate Immunity

2009

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“…TLR3 is especially implicated in sensing viral infections and in activating innate immunity (31,58). PIC has long been known for its ability to induce type I and type II interferons (25), stimulate the cytotoxic activity of NK cells (4,41,59), and increase antiviral and antitumor reactions (26,50,51). Moreover, PIC is a potent activator of adaptive immunity through induction of dendritic cell maturation, regulation of Th1/Th2 responses, and promotion of antigen-specific antibody responses (4,59), and TLR ligands have been suggested to promote GC formation (42).…”

mentioning

confidence: 99%

Toll-Like Receptor 3 Ligand and Retinoic Acid Enhance Germinal Center Formation and Increase the Tetanus Toxoid Vaccine Response

Ross

2009

Clin Vaccine Immunol

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“…PIC is well known for its ability to induce type I͞type II IFNs and enhance antiviral and antitumor reactions in several models (20)(21)(22). Furthermore, PIC is a potent immune adjuvant that can promote dendritic cell (DC) maturation, increase natural killer (NK)-mediated cytotoxicity, and enhance CD8 T cell response as well as T helper (Th) 1-cytokine production (23,24).…”

mentioning

confidence: 99%

The anti-tetanus immune response of neonatal mice is augmented by retinoic acid combined with polyriboinosinic:polyribocytidylic acid

Ross²

2005

Proc. Natl. Acad. Sci. U.S.A.

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Neonates are highly susceptible to infectious diseases and, in general, respond poorly to conventional vaccines due to immaturity of the immune system. In the present study, we hypothesized that the anti-tetanus toxoid (TT) vaccine response of neonatal mice could be enhanced by retinoic acid (RA), a bioactive retinoid, and polyriboinosinic:polyribocytidylic acid (PIC), an inducer of IFN. Early-life treatments with RA and͞or PIC were well tolerated and stimulated both primary anti-TT IgG production in infancy and the memory response in adulthood. TT-specific lymphocyte proliferation and type 1͞type 2 cytokine production were also significantly augmented.

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Immunoprophylactic strategies against respiratory influenza virus infection

Cited by 15 publications

References 22 publications

siRNA and Innate Immunity

siRNA and Innate Immunity

Toll-Like Receptor 3 Ligand and Retinoic Acid Enhance Germinal Center Formation and Increase the Tetanus Toxoid Vaccine Response

The anti-tetanus immune response of neonatal mice is augmented by retinoic acid combined with polyriboinosinic:polyribocytidylic acid

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