Human papillomavirus-like particles mediate functional delivery of plasmid DNA to antigen presenting cells in vivo.
Because recombinant empty viral capsids are potentially attractive vectors for gene therapy, here we examined the ability of human papillomavirus (HPV) virus-like particles (VLPs) to mediate delivery and expression of DNA plasmids in vitro and in vivo. VLP-mediated delivery and expression of a GFP reporter construct in vitro was found to be highly dependent upon the presence of full-length L2 protein within the VLPs. Similarly, expression of GFP and luciferase reporter plasmids in vivo was strongly enhanced by co-administration of L1/L2 VLPs. Interestingly, in these experiments we routinely observed GFP expression in migrating antigen presenting cells (APC) recovered from mice inoculated with GFP plasmid in combination with VLPs, but not in APC recovered from mice inoculated with the plasmid alone. Additional evidence to support this concept was generated in experiments in which co-administration of VLPs with a plasmid designed to express HPV16 E6 oncoprotein was associated with significant enhancement of plasmid-encoded E6-specific cellular immune responses. These findings have implications for the design of vaccines for combined prophylaxis and therapy of HPV-associated diseases, and for other vaccines that rely on the administration of DNA-based immunogens, adjuvants, and/or other factors.
Malboeuf
Christine M
CM
Department of Medicine, University of Rochester School of Medicine and Dentistry, NY 14642, USA.
Simon
David A L
DA
Lee
Young-Eun Ellen
YE
Lankes
Heather A
HA
Dewhurst
Stephen
S
Frelinger
John G
JG
Rose
Robert C
RC
D000818:Animals; D000938:Antigen-Presenting Cells / Q000378:metabolism*; D036022:Capsid Proteins / Q000502:physiology; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D049452:Green Fluorescent Proteins / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology / Q000502:physiology; D027383:Papillomaviridae / Q000235:genetics*; D010957:Plasmids; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology; D014771:Virion / Q000235:genetics*
D036022:Capsid Proteins; C068651:E6 protein, Human papillomavirus type 16; C063316:L2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D049452:Green Fluorescent Proteins; C063317:L1 protein, Human papillomavirus type 16