AUTO/ALLOCELL-HIV - Development of a novel therapeutic HIV-1 vaccine: Horizontal gene transfer by using apoptotic HIV-1 DNA containing activated T cells (Life sciences, genomics and biotechnology for health) (2006-01-01 - 2008-12-31)(»add to infobox)
ACRONYM:
AUTO/ALLOCELL-HIV
BUDGET:
2.878.490 €
FUNDING:
1.690.730 €
INSTRUMENT:
Specific Targeted Research Project
PROGRAMME:
Life sciences, genomics and biotechnology for health
The overall objective for this multidisciplinary consortium is to transfer to the clinic our basic discovery that genes can be horizontally transferred to neighbouring cells by uptake of apoptotic cells. Our goal is to develop a therapeutic HIV-1 vaccine based on this technology. Apoptotic cells can be a good antigen delivery system by utilizing the body´s own natural mechanisms for transfer of DNA and proteins to antigen presenting cells (APC). Normally during HIV-1 infection this system is hindered by multiple mechanisms. We therefore envisage using this system during periods of low viral replication achieved by antiretroviral treatment. Hence, we will immunize already infected individuals who have received a limited period of antiretroviral treatment with either autologous apoptotic HIV-1 infected cells (AutoCell-HIV) or allogeneic apoptotic HIV-1 pseudovirus containing cells (AlloCell-HIV). The advantages with the present technology are; i)Antigen is targeted to the APC where it is expressed a for long time period. ii)In a mouse model broad cellular and humoral immune responses are generated after immunizations using this strategy. iii)The ¿vector¿ i.e the apoptotic infected cell, is capable of activating dendritic cells leading to stimulation of T cells. iv) The therapy is individualized and contains viral sequences from the patients own virus. v) HIV-1 genes and antigens are transferred to APC in a milieu devoid of viral replication vi) We immunize with apoptotic cells directly and hence do not require culturing of dendritic cells, which would be more cumbersome and therefore more difficult to implement in the developing world. We will perform safety and immunogenicity studies in macaques. We will optimize techniques for production of AutoCell and AlloCell in a Good Manufacturing Practice (GMP) certified Cell Therapy Center. We will produce individualized prototype AutoCell compositions and launch a Phase I/II clinical trial.
