Liposome-mediated immunotherapy against respiratory influenza virus infection using double-stranded RNA poly ICLC

Wong, Jonathan P.; Yang, Huanming; Nagata, Les P.; Kende, Meir; Levy, Hilton B.; Schnell, Glen; Blasetti, Karen

doi:10.1016/s0264-410x(98)00439-3

Cited by 42 publications

(47 citation statements)

References 9 publications

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“…Such targeted immunostimulation may help to boost antiviral immunity in the airways of patients suffering from postviral exacerbations of underlying lung disease, such as cystic fibrosis. Prior animal studies favorably assessed the ability of different formulations of poly(I:C) to augment antiviral defenses and facilitate viral clearance in the airways (43)(44)(45)(46)(47)(48). However, potential inflammagenic effects of such immunostimulation have not been extensively addressed.…”

Section: Discussionmentioning

confidence: 99%

Stimulation of the RIG-I/MAVS Pathway by Polyinosinic:Polycytidylic Acid Upregulates IFN-β in Airway Epithelial Cells with Minimal Costimulation of IL-8

Dauletbaev

Cammisano

Herscovitch

et al. 2015

The Journal of Immunology

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Pharmacological stimulation of the antiviral cytokine IFN-β in the airways may help to counter deleterious virus-induced exacerbations in chronic inflammatory lung diseases (asthma, chronic obstructive pulmonary disease, or cystic fibrosis). Polyinosinic-polycytidylic acid [poly(I:C)] is a known inducer of IFN-β but also costimulates an inflammatory response. The latter response is undesirable given the pre-existing airway inflammation in these diseases. The objective of our study was to identify conditions for poly(I:C) to selectively upregulate IFN-β in airway epithelial cells without a concomitant inflammatory response. The inflammatory response was gauged by production of the chemokine IL-8. Using cell lines and primary airway epithelial cells (both submerged and well-differentiated), we observed that pure poly(I:C) stimulated IFN-β mainly through the TLR3/TRIF pathway and IL-8 through an unidentified pathway. The magnitude of the IL-8 response stimulated by pure poly(I:C) matched or even exceeded that of IFN-β. Furthermore, this IL-8 response could not be pharmacologically downregulated without affecting IFN-β. In contrast, we show that stimulation of the RIG-I/MAVS pathway, such as when poly(I:C) is delivered intracellularly in a complex with liposomes or via nucleofection, selectively stimulates IFN-β with low IL-8 costimulation. The magnitude of IFN-β stimulation by liposome-encapsulated poly(I:C) is markedly diminished in well-differentiated cells. In conclusion, it is feasible to augment IFN-β production in airway epithelial cells without excessive costimulation of IL-8 if the RIG-I/MAVS pathway is stimulated, such as via liposomal delivery of poly(I:C). Better cytoplasmic delivery vehicles are needed to efficiently stimulate this pathway in well-differentiated cells.

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Section: Discussionmentioning

confidence: 99%

Stimulation of the RIG-I/MAVS Pathway by Polyinosinic:Polycytidylic Acid Upregulates IFN-β in Airway Epithelial Cells with Minimal Costimulation of IL-8

Dauletbaev

Cammisano

Herscovitch

et al. 2015

The Journal of Immunology

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“…In fact, even mammalian DNA becomes a potent immune stimulant when combined with cationic liposomes, as demonstrated recently in a murine tumor model (34). Moreover, cationic liposomes can be used to potentiate immune activation by other TLR agonists, including the TLR3 agonist polyI:C and TLR7/8 agonists such as single-stranded RNA (35)(36)(37)(38).…”

Section: Liposomes Enhance Innate Immune Activation By Nucleic Acidsmentioning

confidence: 96%

“…Significant protection from experimental influenza virus infection in mice has also been achieved using cationic liposomes complexed to a synthetic double-strand RNA mimic (poly ICLC) (36). In that model, durable, complete protection from lethal virus challenge could be achieved by intransal administration of the liposome-poly ICLC complexes up to 3 weeks prior to virus challenge.…”

Section: Antiviral Immunotherapy With Cldcmentioning

confidence: 99%

Liposome–nucleic acid immunotherapeutics

Dow¹

2007

Expert Opinion on Drug Delivery

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Cationic liposome-nucleic acid complexes, which were originally developed for use as non-viral gene delivery vectors, may now have an equally important application as immunotherapeutic drugs. Recent studies have highlighted the ability of cationic liposomes to markedly potentiate activation of the innate immune system by certain Toll-like receptor (TLR) agonists. The immune enhancing properties of cationic liposomes are most obvious when they are combined with nucleic acid agonists for endosomally-located TLRs, including TLR3, TLR7/8, and TLR9. How this immune potentiation by cationic liposomes is mediated is not completely understood, but is thought to reflect the combined effects of more efficient endosomal targeting, protection from extracellular degradation, and signaling through newly identified cytoplasmic receptors for nucleic acids. The potent innate immune stimulatory properties of liposome-nucleic acid complexes make them particularly effective as immunotherapeutics or vaccine adjuvants. As stand-alone immunotherapeutics, liposome-nucleic acid complexes have demonstrated impressive anti-cancer activity in a number of different animal tumor models. Moreover, liposome-nucleic acid complexes also show promise for immunotherapy of acute viral and bacterial infections and chronic fungal infections. When used as vaccine adjuvants, liposome-nucleic acid complexes target antigens for efficient uptake by dendritic cells and are particularly effective in eliciting T cell responses. Thus, cationic liposomes combined with nucleic acids form the basis for a potent and versatile immunotherapeutic platform.

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“…The development of needle-free vaccines has been hindered by the lack of safe adjuvants, because traditional mucosal adjuvants, such as poly(I:C), have been associated with serious side effects in mice and humans (37,49 tive mucosal adjuvants, with few side effects in the animal models. We previously showed that mice that received three daily doses of 100 g of PIKA intranasally showed no significant weight loss (25a).…”

Section: ͻ1:33 Had No Virus Detectable In the Lungsmentioning

confidence: 99%

An Adjuvant for the Induction of Potent, Protective Humoral Responses to an H5N1 Influenza Virus Vaccine with Antigen-Sparing Effect in Mice

Lau

Tang

McCall

et al. 2010

J Virol

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Intramuscular administration of inactivated influenza virus vaccine is the main vaccine platform used for the prevention of seasonal influenza virus infection. In clinical trials, inactivated H5N1 vaccines have been shown to be safe and capable of eliciting immune correlates of protection. However, the H5N1 vaccines are poorly immunogenic compared to seasonal influenza virus vaccines. Needle-free vaccination would be more efficient and economical in a pandemic, and the development of an effective and safe mucosal adjuvant will be an important milestone. A stabilized chemical analog of double-stranded RNA, PIKA, was previously reported to be a potent mucosal adjuvant in a murine model. While PIKA stimulates dendritic cells in vitro, little was known about its receptor and adjuvanting mechanism in vivo. In this study, we demonstrated that the immunostimulatory effect of PIKA resulted in an increased number of mature antigen-presenting cells, with the induction of proinflammatory cytokines at the inoculation site. In addition, coadministration of PIKA with a poorly immunogenic H5N1 subunit vaccine led to antigen sparing and quantitative and qualitative improvements of the immune responses over those achieved with an unadjuvanted vaccine in mice. The adjuvanted vaccine provided protection against lethal challenge with homologous and heterologous H5N1 wild-type viruses. Mice lacking functional TLR3 showed diminished cytokine production with PIKA stimulation, diminished antibody responses, and reduced protective efficacy against wild-type virus challenge following vaccination. These data suggest that TLR3 is important for the optimal performance of PIKA as an adjuvant. With its good safety profile and antigen-sparing effect, PIKA could be an attractive adjuvant for use in future pandemics.

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Liposome-mediated immunotherapy against respiratory influenza virus infection using double-stranded RNA poly ICLC

Cited by 42 publications

References 9 publications

Stimulation of the RIG-I/MAVS Pathway by Polyinosinic:Polycytidylic Acid Upregulates IFN-β in Airway Epithelial Cells with Minimal Costimulation of IL-8

Stimulation of the RIG-I/MAVS Pathway by Polyinosinic:Polycytidylic Acid Upregulates IFN-β in Airway Epithelial Cells with Minimal Costimulation of IL-8

Liposome–nucleic acid immunotherapeutics

An Adjuvant for the Induction of Potent, Protective Humoral Responses to an H5N1 Influenza Virus Vaccine with Antigen-Sparing Effect in Mice

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