Current Gene Therapy

Ignacio Anegon
Director INSERM UMR 1064-Center for Research in Transplantation and Immunology
CHU de Nantes. 30, boulevard
Nantes
France

Back

Adenoviral Gene Delivery for HIV-1 Vaccination

Author(s): T. Vanniasinkam, H. C.J. Ertl.

Abstract:

The AIDS epidemic continues to spread throughout nations of Africa and Asia and is by now threatening to undermine the already frail infrastructure of developing countries in Sub-Saharan Africa that are hit the hardest. The only option to stem this epidemic is through inexpensive and efficacious vaccines that prevent or at least blunt HIV-1 infections. Despite decades of pre-clinical and clinical research such vaccines remain elusive. Most anti-viral vaccines act by inducing protective levels of virus-neutralizing antibodies. The envelope protein of HIV-1, the sole target of neutralizing antibodies, is constantly changing due to mutations, B cell epitopes are masked by heavy glycosylation and the proteins structural unfolding upon binding to its CD4 receptor and chemokine co-receptors. Efforts to induce broadly crossreactive virus-neutralizing antibodies able to induce sterilizing or near sterilizing immunity to HIV-1 have thus failed. Studies have indicated that cell-mediated immune responses and in particular CD8+ T cell responses to internal viral proteins may control HIV-1 infections without necessarily preventing them. Adenoviral vectors expressing antigens of HIV-1 are eminently suited to stimulate potent CD8+ T cell responses against transgene products, such as antigens of HIV-1. They performed well in pre-clinical studies in rodents and nonhuman primates and are currently in human clinical trials. This review summarizes the published literature on adenoviral vectors as vaccine carriers for HIV-1 and discusses advantages and disadvantages of this vaccine modality.

Keywords: Highly active antiretroviral therapy, pro-inflammatory cytokines, antigens, gag proteins, modified vaccinia Ankora, t cell responses, dna vaccines, adenoviral vectors, immunogenicity, hiv-1

Order Reprints Order Eprints Rights & PermissionsPrintExport

Article Details

VOLUME: 5
ISSUE: 2
Year: 2005
Page: [203 - 212]
Pages: 10
DOI: 10.2174/1566523053544236
Price: $58