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


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.
Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Yi
Y
Li
Yanxin
Y
Hu
Yi
Y
Jin
Guozhong
G
Zhang
Jonathan
J
Wong
Lun-Quan
LQ
Sun
Ming
M
Wang
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002266:Carboxymethylcellulose Sodium / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D016207:Cytokines / Q000276:immunology; D004285:Dogs; D005260:Female; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology* / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology; D008081:Liposomes / Q000378:metabolism; D008168:Lung / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D011070:Poly I-C / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D011107:Polylysine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology / Q000494:pharmacology; D012330:RNA, Double-Stranded / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology; D015164:Vaccines, Inactivated / Q000276:immunology; D014779:Virus Replication
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D016207:Cytokines; D007252:Influenza Vaccines; D008081:Liposomes; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D015164:Vaccines, Inactivated; D011107:Polylysine; C019531:poly ICLC; D002266:Carboxymethylcellulose Sodium; D011070:Poly I-C