DermaVir: a novel topical vaccine for HIV/AIDS.
Human immunodeficiency virus (HIV) vaccines have the potential to improve antiretroviral drug treatment by inducing cytotoxic killing of HIV-infected cells. Prophylactic vaccines utilize new antigens to initiate immunity; however, in HIV-infected individuals the load of viral antigen is not the limiting factor for the restoration of immune responses. Here we describe a novel immunization strategy with DermaVir that improves viral antigen presentation using dendritic cells (DC). DermaVir contains a distinctive plasmid DNA expressing all HIV proteins except integrase to induce immune responses with broad specificity. The DNA is formulated to a mannosilated particle to target antigen-presenting cells and to protect the DNA from intracellular degradation. After topical application, DermaVir-transduced cells migrate from the skin to the draining lymph node and interdigitate as DermaVir-expressing, antigen-presenting DC. We compared the immunogenicity of topical and ex vivo DC-based DermaVir vaccinations in naive rhesus macaques. Both vaccinations induced simian immunodeficiency virus-specific CD4 helper and CD8 memory T cells detected by an in vivo skin test and an in vitro intracellular cytokine-based assay. Topical DermaVir vaccination represents an improvement upon existing ex vivo DC-based immunization technologies and may provide a new therapeutic option for HIV-infected patients.
Lisziewicz
Julianna
J
Research Institute for Genetic and Human Therapy (RIGHT), Washington, DC 20007, USA. lisziewj@geneticimmunity.com
Trocio
Jeffrey
J
Whitman
Lucia
L
Varga
Georg
G
Xu
Jianqing
J
Bakare
Nyasha
N
Erbacher
Patrick
P
Fox
Cecil
C
Woodward
Ruth
R
Markham
Phil
P
Arya
Suresh
S
Behr
Jean-Paul
JP
Lori
Franco
F
D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology*; D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control*; D000287:Administration, Topical; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008253:Macaca mulatta; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids; D018417:Th1 Cells / Q000276:immunology; D014611:Vaccination / Q000379:methods
D016915:AIDS Vaccines