Abstract
Methods In our view, three parameters are critical for the generation of potent ex vivo-generated DC vaccines for HIV patients: 1) antigen; 2) DC type; and 3) activation signal. With this in mind, we designed a clinical trial (IRB#008017; BB-IND #13748) to test the safety and immune efficacy of a therapeutic HIV vaccine consisting of autologous DCs generated ex vivo from monocytes cultured with GMCSF/IFN-alpha and loaded with five lipidated HIV antigens (LIPO5). Our trial exploits a combination of: 1) HIVderived lipopeptides that cover nef, gag and pol epitopes – binding to >90% of HLA molecules and permitting presentation of T cell epitopes and generation of humoral immunity; 2) Interferon (IFN)-DCs, which demonstrate powerful priming functions in vitro; and 3) LPS activation, which enhances priming by IFN-DCs. Such a vaccine is expected to induce strong and diverse HIV-specific immune responses. Results This phase I clinical trial in 19 asymptomatic HIV-infected patients with undetectable viral load while treated with HAART will test the safety of DC vaccination and of analytical treatment interruption (ATI). Patients receive four monthly DC vaccinations in conjunction with antiretroviral therapy. Twelve weeks after the fourth vaccine, patients who meet the pre-specified criteria will stop HAART. ATI will last for up to six months.
Highlights
The advent of highly active antiretroviral therapies (HAART) changed the course of human immunodeficiency virus (HIV) infection
Vaccines act via dendritic cells (DCs), which induce, regulate and maintain immune responses
Three parameters are critical for the generation of potent ex vivo-generated DC vaccines for HIV patients: 1) antigen; 2) DC type; and 3) activation signal
Summary
DALIA: dendritic cell and lipopeptide-induced immunity against AIDS: a phase I trial. J Banchereau, C Harrod*1, A Cobb, G Chene, L Sloan, K Palucka, Y Levy and DALIA Team. Address: 1Baylor Institute for Immunology Research (INSERM Unit 899), Dallas, TX, USA, 2Institut de Santé Publique, d'Epidémiologie et de Developpement, Bordeaux, France, 3North Texas Infectious Diseases Clinic, Dallas, TX, USA and 4Agence Nationale de Recherche sur le Sida et les hépatites virales, Paris, France. Published: 22 October 2009 Retrovirology 2009, 6(Suppl 3):P320 doi:10.1186/1742-4690-6-S3-P320. AIDS Vaccine 2009 Anna Laura Ross Meeting abstracts – A single PDF containing all abstracts in this Supplement is available here. http://www.biomedcentral.com/content/pdf/1471-2105-10-S12-info.pdf
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