Immunity against both polyomavirus VP1 and a transgene product induced following intranasal delivery of VP1 pseudocapsid-DNA complexes.
Murine polyomavirus VP1 virus-like particles (VLPs) can bind plasmid DNA and transport it into cells both in vitro and in vivo. Long-term expression of the transgene can be observed, suggesting that VP1 VLPs may be used as DNA delivery vehicles for gene therapy. In this study we have analysed the in vitro efficiency of transfection using different DNA/VLP molar ratios and the immune response induced following intranasal administration of these complexes to mice. Our results indicate that in short-term in vitro culture VP1 VLP-DNA complexes appear to be as efficient as DNA alone at transfecting cell monolayers. They also show that VP1 VLPs are very immunogenic, inducing high proliferative cell responses and both serum and mucosal antibodies. Moreover, VP1 VLP-DNA complexes appear to be capable of inducing a stronger immune response to the transgene product (beta-galactosidase) than immunization with DNA only. The results suggest that polyomavirus VP1 VLPs derived from the wild-type sequence may be too immunogenic for repeated use as gene delivery vehicles in gene therapy. However, due to their high immunogenicity and apparent adjuvant properties, they could be modified and used as vaccines either on their own or complexed with DNA.
Clark
B
B
Viral Oncology Unit, Division of Medicine, ICSM at St Mary's Hospital1, BS-ICSM at St Mary's Hospital2, Norfolk Place, London W2 1PG, UK.
Caparrós-Wanderley
W
W
Viral Oncology Unit, Division of Medicine, ICSM at St Mary's Hospital1, BS-ICSM at St Mary's Hospital2, Norfolk Place, London W2 1PG, UK.
Musselwhite
G
G
Viral Oncology Unit, Division of Medicine, ICSM at St Mary's Hospital1, BS-ICSM at St Mary's Hospital2, Norfolk Place, London W2 1PG, UK.
Kotecha
M
M
Division of Life Sciences, Franklin-Wilkins Building, King's College London, 150 Stamford Street, London SE1 8WA, UK3.
Griffin
B E
BE
Viral Oncology Unit, Division of Medicine, ICSM at St Mary's Hospital1, BS-ICSM at St Mary's Hospital2, Norfolk Place, London W2 1PG, UK.
D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000097:blood; D019556:COS Cells; D002213:Capsid / Q000276:immunology* / Q000378:metabolism; D036022:Capsid Proteins; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000378:metabolism; D014162:Transfection; D019076:Transgenes; D014771:Virion / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D001616:beta-Galactosidase / Q000235:genetics / Q000276:immunology*
D000914:Antibodies, Viral; D036022:Capsid Proteins; D004279:DNA, Viral; C062481:VP1 protein, polyomavirus; D001616:beta-Galactosidase