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

Abstract

BACKGROUND:

In view of the magnitude and severity of outbreaks of the highly pathogenic H5N1 influenza virus (H5N1-HPIV) and the threat to public health, there is an urgent need to develop broad-spectrum prophylactic and therapeutic agents against infection by H5N1-HPIV and other subtypes.

METHODS AND RESULTS:

In the present study, we explored the use of LE-PolyICLC, a liposome encapsulated double-stranded RNA, as a possible prophylactic, therapeutic and immune enhancement agent. In a mouse infection model, we showed that the administration of LE-PolyICLC intranasally before or shortly after infection could inhibit virus replication, leading to a significant reduction in pulmonary viral titres and a higher survival rate of infected mice. When used as a molecular adjuvant, LE-PolyICLC significantly enhanced both the humoral and cellular responses elicited by inactivated H5N1 vaccine and augmented the protective efficacy provided by vaccination. Most importantly, the data also demonstrate that LE-PolyICLC could effectively attenuate the development of pulmonary fibrosis during the restoration period at day 14 after H5N1 infection.

CONCLUSIONS:

Taken together, the data obtained in the present study suggest that strong consideration should be given for the use of LE-PolyICLC as prophylactic and therapeutic agents and also as a vaccination adjuvant to combat highly pathogenic influenza infection and its associated complications such as pulmonary fibrosis.

• Authors: Yi Li, Yanxin Hu, Yi Jin, Guozhong Zhang, Jonathan Wong, Lun-Quan Sun, Ming Wang
• Journal: The journal of gene medicine (J Gene Med) Vol. 13 Issue 1 Pg. 60-72 (Jan 2011) ISSN: 1521-2254 [Electronic] England
• PMID: 21259409 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 John Wiley & Sons, Ltd.

Chemical References

• Adjuvants, Immunologic
• Antibodies, Viral
• Cytokines
• Influenza Vaccines
• Liposomes
• RNA, Double-Stranded
• RNA, Viral
• Vaccines, Inactivated
• Polylysine
• poly ICLC
• Carboxymethylcellulose Sodium
• Poly I-C

Topics

• Adjuvants, Immunologic (administration & dosage, pharmacology)
• Animals
• Antibodies, Viral (blood)
• Carboxymethylcellulose Sodium (administration & dosage, analogs & derivatives, pharmacology)
• Cytokines (immunology)
• Dogs
• Female
• Influenza A Virus, H5N1 Subtype (immunology, pathogenicity)
• Influenza Vaccines (administration & dosage, immunology)
• Liposomes (metabolism)
• Lung (pathology, virology)
• Mice
• Mice, Inbred BALB C
• Orthomyxoviridae Infections (immunology, prevention & control)
• Poly I-C (administration & dosage, immunology, pharmacology)
• Polylysine (administration & dosage, analogs & derivatives, immunology, pharmacology)
• RNA, Double-Stranded (analysis)
• RNA, Viral (analysis)
• T-Lymphocytes (immunology)
• Vaccines, Inactivated (immunology)
• Virus Replication