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 limi...

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Bibliographic Details
Published in:Journal of investigative dermatology 2005-01, Vol.124 (1), p.160-169
Main Authors: Lisziewicz, Julianna, Trocio, Jeffrey, Whitman, Lucia, Varga, Georg, Xu, Jianqing, Bakare, Nyasha, Erbacher, Patrick, Fox, Cecil, Woodward, Ruth, Markham, Phil, Arya, Suresh, Behr, Jean-Paul, Lori, Franco
Format: Article
Language:English
Subjects:
Acquired Immunodeficiency Syndrome - immunology
Acquired Immunodeficiency Syndrome - prevention & control
Administration, Topical
AIDS Vaccines - genetics
AIDS Vaccines - immunology
AIDS Vaccines - pharmacology
Animals
Antigen Presentation - genetics
Antigen Presentation - immunology
Biological and medical sciences
cellular immunity
dendritic cells
Dendritic Cells - immunology
Dermatology
Female
Gene Expression Regulation, Viral - immunology
Human immunodeficiency virus
Human viral diseases
Infectious diseases
Lymph Nodes - cytology
Lymph Nodes - immunology
Macaca mulatta
Medical sciences
Mice
Mice, Inbred BALB C
Plasmids
skin
Th1 Cells - immunology
therapy
topical vaccine
Vaccination - methods
Viral diseases
Viral diseases of the lymphoid tissue and the blood. Aids
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Description
Summary: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 naïve 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.
ISSN:0022-202X
1523-1747
DOI:10.1111/j.0022-202X.2004.23535.x