Prophylactic effects of chitin microparticles on highly pathogenic H5N1 influenza virus

Abstract

Highly pathogenic avian influenza virus (H5N1) is an emerging pathogen with the potential to cause great harm to humans, and there is concern about the potential for a new influenza pandemic. This virus is resistant to the antiviral effects of interferons and tumor necrosis factor-alpha. However, the mechanism of interferon-independent protective innate immunity is not well understood. The prophylactic effects of chitin microparticles as a stimulator of innate mucosal immunity against a recently obtained strain of H5N1 influenza virus infection were examined in mice. Clinical parameters and the survival rate of mice treated by intranasal application of chitin microparticles were significantly improved compared to non-treated mice after a lethal influenza virus challenge. Flow cytometric analysis revealed that the number of natural killer cells that expressed tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and that had migrated into the cervical lymph node was markedly increased (26-fold) after intranasal treatment with chitin microparticles. In addition, the level of IL-6 and interferon-gamma-inducible protein-10 (IP-10) in the nasal mucosa after H5N1 influenza virus challenge was decreased by prophylactic treatment with chitin microparticles. These results suggest that prophylactic intranasal administration of chitin microparticles enhanced the local accumulation of natural killer cells and suppressed hyper-induction of cytokines, resulting in an innate immune response to prevent pathogenesis of H5N1 influenza virus.

Innate sensors of influenza virus: clues to developing better intranasal vaccines

“…Although CT and LT are effective adjuvants to enhance mucosal immune responses including sIgA responses, they have some side effects in humans, including Bell’s palsy and nasal discharge [94,95]. Therefore, other adjuvants that are as effective as CT or LT and are also safe for human use have been developed for clinical application with intranasal influenza vaccine [51–53,96–102]. …”

Purification and characterization of an exo-type β-N-acetylglucosaminidase from Pseudomonas fluorescens JK-0412

“…Chitin and its derivatives are known to exhibit many biological properties such as immune‐modulating (Shibata et al. 2001; Ichinohe et al. 2007), anticholesterolaemic (Muzzarelli 1997), anti‐inflammatory (Valdivia et al.…”

Attenuated Bordetella pertussis Protects against Highly Pathogenic Influenza A Viruses by Dampening the Cytokine Storm

“…Reduced immunopathology, together with lower levels of IL-6 production but also with reduced viral loads, was observed with the protected mice compared to the control mice. In another report, prophylactic intranasal treatment with chitin microparticles enhanced the local accumulation of NK cells and suppressed hyperinduction of cytokines, resulting in pro- (22). However, in both studies, the prophylactic treatment needed to be performed less than a few days prior to the virus challenge in order to be protective, resulting in a transient, short-term downregulation of the host inflammatory response.…”