Prophylactic, therapeutic and immune enhancement effect of liposome‐encapsulated PolyICLC on highly pathogenic H5N1 influenza infection

Li, Yi; Hu, Yanxin; Jin, Yi; Zhang, Guozhong; Wong, Jonathan P.; Sun, Lun‐Quan; Wang, Ming

doi:10.1002/jgm.1536

Cited by 19 publications

(10 citation statements)

References 37 publications

(34 reference statements)

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“…Imiquimod and gardiquimod (R848) activate TLR7, which recognizes single-stranded RNA [17], [18]. Both Poly I:C and TLR7 agonists are being considered as therapeutic or preventive agents for combating a variety of respiratory pathogens of pandemic or bioterrorism potential, including pandemic influenza, H5N1 avian flu, and Francisella tularensis , as they are believed to be an effective and safe “booster” of antiviral immune responses [19], [20], [21], [22]. In our murine model of pulmonary infection, we administered poly I:C or TLR7 agonist intranasally, followed by intratracheal challenge with common respiratory pathogens that cause postinfluenza bacterial pneumonia, to determine whether stimulation of antiviral immune pathways would increase susceptibility to secondary bacterial infection.…”

Section: Introductionmentioning

confidence: 99%

Poly I:C Enhances Susceptibility to Secondary Pulmonary Infections by Gram-Positive Bacteria

Tian

Lung

et al. 2012

PLoS ONE

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Secondary bacterial pneumonias are a frequent complication of influenza and other respiratory viral infections, but the mechanisms underlying viral-induced susceptibility to bacterial infections are poorly understood. In particular, it is unclear whether the host's response against the viral infection, independent of the injury caused by the virus, results in impairment of antibacterial host defense. Here, we sought to determine whether the induction of an “antiviral” immune state using various viral recognition receptor ligands was sufficient to result in decreased ability to combat common bacterial pathogens of the lung. Using a mouse model, animals were administered polyinosine-polycytidylic acid (poly I:C) or Toll-like 7 ligand (imiquimod or gardiquimod) intranasally, followed by intratracheal challenge with Streptococcus pneumoniae. We found that animals pre-exposed to poly I:C displayed impaired bacterial clearance and increased mortality. Poly I:C-exposed animals also had decreased ability to clear methicillin-resistant Staphylococcus aureus. Furthermore, we showed that activation of Toll-like receptor (TLR)3 and Retinoic acid inducible gene (RIG-I)/Cardif pathways, which recognize viral nucleic acids in the form of dsRNA, both contribute to poly I:C mediated impairment of bacterial clearance. Finally, we determined that poly I:C administration resulted in significant induction of type I interferons (IFNs), whereas the elimination of type I IFN signaling improved clearance and survival following secondary bacterial pneumonia. Collectively, these results indicate that in the lung, poly I:C administration is sufficient to impair pulmonary host defense against clinically important gram-positive bacterial pathogens, which appears to be mediated by type I IFNs.

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Section: Introductionmentioning

confidence: 99%

Poly I:C Enhances Susceptibility to Secondary Pulmonary Infections by Gram-Positive Bacteria

Tian

Lung

et al. 2012

PLoS ONE

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“…In murine vaccination models, dose levels of 50 µg (administered subcutaneously) were administered with a malaria vaccine [33], [53]. A liposome-encapsulated form of polyICLC was also tested with intranasal administration in mice, wherein a dose of 20 µg of polyICLC increased the efficacy of an H5N1 vaccine [54]. In NHP, our group has utilized 100 µg of polyICLC as an adjuvant with the VLP with great success [55], but 1 to 3 mg of polyICLC or polyIC is commonly used in NHP vaccination studies [24], [33]–[35].…”

Section: Discussionmentioning

confidence: 99%

Toll-Like Receptor Agonist Augments Virus-Like Particle-Mediated Protection from Ebola Virus with Transient Immune Activation

et al. 2014

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Identifying safe and effective adjuvants is critical for the advanced development of protein-based vaccines. Pattern recognition receptor (PRR) agonists are increasingly being explored as potential adjuvants, but there is concern that the efficacy of these molecules may be dependent on potentially dangerous levels of non-specific immune activation. The filovirus virus-like particle (VLP) vaccine protects mice, guinea pigs, and nonhuman primates from viral challenge. In this study, we explored the impact of a stabilized dsRNA mimic, polyICLC, on VLP vaccination of C57BL/6 mice and Hartley guinea pigs. We show that at dose levels as low as 100 ng, the adjuvant increased the efficacy of the vaccine in mice. Antigen-specific, polyfunctional CD4 and CD8 T cell responses and antibody responses increased significantly upon inclusion of adjuvant. To determine whether the efficacy of polyICLC correlated with systemic immune activation, we examined serum cytokine levels and cellular activation in the draining lymph node. PolyICLC administration was associated with increases in TNFα, IL6, MCP1, MIP1α, KC, and MIP1β levels in the periphery and with the activation of dendritic cells (DCs), NK cells, and B cells. However, this activation resolved within 24 to 72 hours at efficacious adjuvant dose levels. These studies are the first to examine the polyICLC-induced enhancement of antigen-specific immune responses in the context of non-specific immune activation, and they provide a framework from which to consider adjuvant dose levels.

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“…Evidence-Based Complementary and Alternative Medicine mice deficient in TNF-, TNF-receptor, IL-6, MIP-1 , and IL-1R or steroid-treated, wild-type mice did not have a survival advantage compared with wild-type mice following H5N1 influenza infection [27,28]. Interestingly, prophylactic treatment of TLR3 agonist PolyICLC, which strongly upregulates cytokine production, provides protection against H1N1 and H5N1 infections [29,30]. These conflicting studies may be explained in that the inflammatory response helps clear the virus, while aggravating host pathological damage.…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory Activity and Protective Effects of Polysaccharide fromEupatorium adenophorumLeaf Extract on Highly Pathogenic H5N1 Influenza Infection

Jin

Zhang

Wan

et al. 2013

Evidence-Based Complementary and Alternative Medicine

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The development of novel broad-spectrum, antiviral agents against H5N1 infection is urgently needed. In this study, we evaluated the immunomodulatory activities and protective effect of Eupatorium adenophorum polysaccharide (EAP) against the highly pathogenic H5N1 subtype influenza virus. EAP treatment significantly increased the production of IL-6, TNF-α, and IFN-γ both in vivo and in vitro as measured by qPCR and ELISA. In a mouse infection model, intranasal administration of EAP at a dose of 25 mg/kg body weight prior to H5N1 viral challenge efficiently inhibited viral replication, decreased lung lesions, and increased survival rate. We further evaluated the innate immune recognition of EAP, as this process is regulated primarily Dectin-1 and mannose receptor (MR). These results indicate that EAP may have immunomodulatory properties and a potential prophylactic effect against H5N1 influenza infection. Our investigation suggests an alternative strategy for the development of novel antiinfluenza agents and benefits of E. adenophorum products.

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Prophylactic, therapeutic and immune enhancement effect of liposome‐encapsulated PolyICLC on highly pathogenic H5N1 influenza infection

Cited by 19 publications

References 37 publications

Poly I:C Enhances Susceptibility to Secondary Pulmonary Infections by Gram-Positive Bacteria

Poly I:C Enhances Susceptibility to Secondary Pulmonary Infections by Gram-Positive Bacteria

Toll-Like Receptor Agonist Augments Virus-Like Particle-Mediated Protection from Ebola Virus with Transient Immune Activation

Immunomodulatory Activity and Protective Effects of Polysaccharide fromEupatorium adenophorumLeaf Extract on Highly Pathogenic H5N1 Influenza Infection

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