At the World Vaccine Congress Lyon 2012, Dr CÃ©cile Bauche joined us from Theravectys to discuss the design and development of a new lentiviral based anti-HIV therapeutic vaccine. Here is a taster of what she covered:
DNA FLAP & LENTIVIRAL VECTORS
â¢Contrary to any other retrovirus, HIV VIRUS IS ABLE TO INFECT ANY NON-DIVIDING CELLS. In 1999, a 99 nucleotides sequence was identified, dubbed DNA Flap or Triplex DNA, which forms during the natural reverse transcription of HIV.
â¢This sequence is necessary for the PRE-INTEGRATION COMPLEX of the virus to cross the membrane of the nucleus of the non-dividing cells it infects. The ability of lentiviral vectors to TRANSDUCE DENDRITIC CELLS IN A STABLE MANNER enables the presentation of antigens in an endogenous way to T cells, thereby allowing the FIRST VACCINE APPLICATIONS TO BE DEVELOPED.
MODE OF ACTION
ENTRY OF THE VECTOR IN A TARGET CELL
The vector encoding THERAVECTYS' antigen enters an immature DC. Uncoating occurs in the cell' cytoplasm followed by reverse transcription.
EXPRESSION OF THE TRANSGENE
After its integration into the genome, the transgene is expressed and processed into epitopes.
PRESENTATION OF THE EPITOPES
The dendritic cell matures and presents the epitopes bound to MHC class I and class II molecules at its surface to specific cytotoxic T lymphocytes (CTLs).
ELIMINATION OF THE TRANSDUCED CELLS
Within a few weeks, the vectors, the transduced cells and the HIV-infected cells are cleared from the body.
PROVE OF CONCEPT : THE MONKEY MODEL
â¢Proof of concept of a PROPHYLACTIC SIV VACCINE in monkeys (cynomolgus) have been performed, and the vaccine efficacy was evaluated during five month, showing (Beignon et al, 2009)
-the INDUCTION of a STRONG T-CELL RESPONSE AGAINST THE GAG antigenic protein,
-a REDUCTION by a factor greater than 100 OF THE VIRAL LOAD at the height of primo infection and,
-a CD4 NON DEPLETION.
Download this presentation to get more in-depth details about design and development of a new lentiviral based anti-HIV therapeutic vaccine
Â· Description of the vectors' features and improvements
Â· Results of the preclinical data
Â· Description of the on-going clinical trial
Dr CÃ©cile Bauche, Chief Scientific Officer, Theravectys
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