Intranasal gene transfer by chitosan-DNA nanospheres protects BALB/c mice against acute respiratory syncytial virus infection.
Respiratory syncytial virus (RSV) infection is often associated in infancy with life-threatening bronchiolitis, which is also a major risk factor for the development of asthma. At present, no effective prophylaxis is available against RSV infection. Herein, we describe an effective prophylactic intranasal gene transfer strategy utilizing chitosan-DNA nanospheres (IGT), containing a cocktail of plasmid DNAs encoding all RSV antigens, except L. A single administration of IGT (25 microg/mouse) induces expression of the mRNA and proteins of all antigens in the lung and results in a significant reduction of viral titers and viral antigen load after acute RSV infection of these mice. IGT-administered mice show no significant change in airway reactivity to methacholine and no apparent pulmonary inflammation. Furthermore, IGT results in significant induction of RSV-specific IgG antibodies, nasal IgA antibodies, cytotoxic T lymphocytes, and interferon-gamma production in the lung and splenocytes compared with controls. Together, these results demonstrate the potential of IGT against acute RSV infection.
Kumar
Mukesh
M
Division of Allergy and Immunology-Joy McCann Culverhouse Airway Disease Center, James A. Haley Veterans Administration Hospital and University of South Florida College of Medicine, Tampa, FL 33612, USA.
Behera
Aruna K
AK
Lockey
Richard F
RF
Zhang
Jian
J
Bhullar
Guraman
G
De La Cruz
Cristina Perez
CP
Chen
Li-Chen
LC
Leong
Kam W
KW
Huang
Shau-Ku
SK
Mohapatra
Shyam S
SS
D000818:Animals; D000956:Antigens, Viral / Q000235:genetics* / Q000276:immunology; D001704:Biopolymers; D002686:Chitin / Q000031:analogs & derivatives*; D048271:Chitosan; D004337:Drug Carriers; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics*; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D012136:Respiratory Syncytial Viruses / Q000235:genetics* / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology; D019562:Viral Load; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology
D000956:Antigens, Viral; D001704:Biopolymers; D004337:Drug Carriers; D019444:Vaccines, DNA; D014765:Viral Vaccines; D002686:Chitin; D007371:Interferon-gamma; D048271:Chitosan