Prophylactic and therapeutic efficacies of poly(IC.LC) against respiratory influenza A virus infection in mice

Wong, Jonathan P.; Saravolac, Edward G.; Sabuda, D; Levy, Hilton B.; Kende, Meir

doi:10.1128/aac.39.11.2574

Cited by 53 publications

(48 citation statements)

References 7 publications

(9 reference statements)

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“…pIC has been reported to protect mice from influenza A virus infection due to its immune-stimulatory properties (30)(31)(32). To determine whether our in vitro-transcribed RIG-I agonist (IVT DI) could also be used as an antiviral, 6-week-old BALB/c mice were inoculated i.n.…”

Section: The In Vitro-transcribed Sev DI Rna Is a Potent Inducer Of Imentioning

confidence: 99%

A Sendai Virus-Derived RNA Agonist of RIG-I as a Virus Vaccine Adjuvant

Martínez-Gil

Goff

Hai

et al. 2013

J Virol

110

115

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The innate immune system is responsible for recognizing invading pathogens and initiating a protective response. In particular, the retinoic acid-inducible gene 1 protein (RIG-I) participates in the recognition of single-and double-stranded RNA viruses. RIG-I activation leads to the production of an appropriate cytokine and chemokine cocktail that stimulates an antiviral state and drives the adaptive immune system toward an efficient and specific response against the ongoing infection. One of the best-characterized natural RIG-I agonists is the defective interfering (DI) RNA produced by Sendai virus strain Cantell. This 546-nucleotide RNA is a well-known activator of the innate immune system and an extremely potent inducer of type I interferon. We designed an in vitro-transcribed RNA that retains the type I interferon stimulatory properties, and the RIG-I affinity of the Sendai virus produced DI RNA both in vitro and in vivo. This in vitro-synthesized RNA is capable of enhancing the production of antiinfluenza virus hemagglutinin (HA)-specific IgG after intramuscular or intranasal coadministration with inactivated H1N1 2009 pandemic vaccine. Furthermore, our adjuvant is equally effective at increasing the efficiency of an influenza A/Puerto Rico/8/34 virus inactivated vaccine as a poly(I·C)-or a squalene-based adjuvant. Our in vitro-transcribed DI RNA represents an excellent tool for the study of RIG-I agonists as vaccine adjuvants and a starting point in the development of such a vaccine.

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Section: The In Vitro-transcribed Sev DI Rna Is a Potent Inducer Of Imentioning

confidence: 99%

A Sendai Virus-Derived RNA Agonist of RIG-I as a Virus Vaccine Adjuvant

Martínez-Gil

Goff

Hai

et al. 2013

J Virol

110

115

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“…These responses provide nonspecific antiviral defense against several viral infections and may therefore provide a broadspectrum antiviral effect against influenza viruses regardless of the strain or subtype involved. 210 Caution is needed with this approach because multiple high doses of poly(I: C) administered intravenously have been found to produce toxic reactions in humans. 211 In addition, poly(I: C) has been observed to stimulate preterm delivery in pregnant mice 71,212 ; therefore, its therapeutic utility during pregnancy is uncertain.…”

Section: Immunotherapymentioning

confidence: 99%

Influenza, Immune System, and Pregnancy

2014

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Influenza is a major health problem worldwide. Both seasonal influenza and pandemics take a major toll on the health and economy of our country. The present review focuses on the virology and complex immunology of this RNA virus in general and in relation to pregnancy. The goal is to attempt to explain the increased morbidity and mortality seen in infection during pregnancy. We discuss elements of innate and adaptive immunity as well as placental cellular responses to infection. In addition, we delineate findings in animal models as well as human disease. Increased knowledge of maternal and fetal immunologic responses to influenza is needed. However, enhanced understanding of nonimmune, pregnancy-specific factors influencing direct interaction of the virus with host cells is also important for the development of more effective prevention and treatment options in the future.

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“…To determine whether SA strains of EEEV are more sensitive to IFN than NA strains in vivo, adult mice were pretreated with several doses of poly(I-C), a potent IFN inducer and immune-modulator known to protect against viral infections (33,39,58). Treatment with poly(I-C) is also simpler to standardize than direct IFN treatment and less expensive, permitting larger sample sizes and greater statistical power.…”

Section: Induction Of Ifn-␣/␤ In Vivomentioning

confidence: 99%

Variation in Interferon Sensitivity and Induction among Strains of Eastern Equine Encephalitis Virus

Aguilar¹,

Paessler

Carrara

et al. 2005

J Virol

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Eastern equine encephalitis virus (EEEV) causes human encephalitis in North America (NA), but in South America (SA) it has rarely been associated with human disease, suggesting that SA strains are less virulent. To evaluate the hypothesis that this virulence difference is due to a greater ability of NA strains to evade innate immunity, we compared replication of NA and SA strains in Vero cells pretreated with interferon (IFN). Human IFN-␣, -␤, and -␥ generally exhibited less effect on replication of NA than SA strains, supporting this hypothesis. In the murine model, no consistent difference in IFN induction was observed between NA and SA strains. After infection with most EEEV strains, higher viremia levels and shorter survival times were observed in mice deficient in IFN-␣/␤ receptors than in wild-type mice, suggesting that IFN-␣/␤ is important in controlling replication. In contrast, IFN-␥ receptor-deficient mice infected with NA and SA strains had similar viremia levels and mortality rates to those of wild-type mice, suggesting that IFN-␥ does not play a major role in murine protection. Mice pretreated with poly(I-C), a nonspecific IFN inducer, exhibited dose-dependent protection against fatal eastern equine encephalitis, further evidence that IFN is important in controlling disease. Overall, our in vivo results did not support the hypothesis that NA strains are more virulent in humans due to their greater ability to counteract the IFN response. However, further studies using a better model of human disease are needed to confirm the results of differential human IFN sensitivity obtained in our in vitro experiments.

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Prophylactic and therapeutic efficacies of poly(IC.LC) against respiratory influenza A virus infection in mice

Cited by 53 publications

References 7 publications

A Sendai Virus-Derived RNA Agonist of RIG-I as a Virus Vaccine Adjuvant

A Sendai Virus-Derived RNA Agonist of RIG-I as a Virus Vaccine Adjuvant

Influenza, Immune System, and Pregnancy

Variation in Interferon Sensitivity and Induction among Strains of Eastern Equine Encephalitis Virus

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