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Development of an hiv vaccine

Prototype hiv vaccines consisting of dna vectors that express either single hiv genes or artificial genes consisting of several genes and gene fragments will be tested for safety, immunogenicity and therapeutic effect in clinical trials and for a therapeutic effect in an animal model.

The aim of the project is to obtain scientific and technological data pertinent for the development of therapeutic HIV (Human Immuno-deficiency Virus) vaccines. The project employs DNA (Deoxyribose Nucleic Acid) vectors for the delivery of the immunogenic antigens, composed of genes or gene fragments from the HIV-1. Two types of DNA vectors will be used: a simplified one containing a promoter for the gene of interest, a bacterial origin of replication and a bacterial selection marker for production of the vaccine in prokaryotic cells and a more complicated one (GTU for Gene Transport Unit) that contains additional elements securing the maintenance and segregation of the plasmid in dividing cell population. Also, in order to avoid the use of antibiotics in the production of the test vaccine, an auxotrophic marker replacing the antibiotic resistant genes has been introduced to GTU. The genes selected for the vaccine consist of non-structural (Rev, Tat and Nef) as well as structural (Gag, Pol, Env) genes of HIV-1. Furthermore, a combination of vaccines representing different HIV sub-types will be used in order to tackle the problem of high variability of the virus, caused by the infidelity of the reverse transcriptase enzyme and leading to up to 20 % variation between different HIV subtypes (Clades A-K). All vaccines within the project have already undergone a robust set of preclinical testing for safety and immunogenicity. Furthermore, some of the candidate vaccines have been tested for safety and immunogenicity in clinical phase I trials in HIV infected and non-infected individuals. The project will comprise different phases which are briefly described below: 1) Testing the immunogenicity and therapeutic effect of the test vaccines in animal models. Different doses and routes of administration of individual plasmids, as well as the use of adjuvants and devices will be tested. Different immunisation regimens comprising priming with DNA and boosting with different proteins will be evaluated in preclinical settings. These studies will be jointly performed in collaboration with KI and SBL Vaccin AB. A model employing a MuLV pseudo-type as an infection model will be used to test the therapeutic capacity of the test vaccines. In collaboration with KI the potency assay of the newly developed vaccine constructs will be established. 2) Evaluation of the pharmacokinetic and toxicological properties of the test vaccines. Repeated dose toxicity, safety pharmacology core battery and bio-distribution studies will be performed in accredited GLP (Good Laboratory Practice) laboratories. 3) Fermentation, purification and aseptic manufacturing of the test vaccines will be optimised and scaled up to ensure sufficient clinical trial material supplies up to II clinical trials and large scale manufacturing processes for DNA plasmid vectors (FIT BIOTECH & VECURA) and HIV peptides linked to the recombinant Cholera Toxin B subunit (SBL VACCIN AB). 4) Testing the test vaccines in Phase I and II therapeutic clinical trials. In the therapeutic trials, the vaccinees will be monitored for the changes in immune response against HIV and also for clinical parameters, such as viral loads and CD4 values. Keywords: HIV-Vaccine (Human Immuno-deficiency Virus), safety, immunogenicity.
Project ID: 
3 421
Start date: 
01-03-2004
Project Duration: 
46months
Project costs: 
13 300 000.00€
Technological Area: 
Virus, Virology, Vaccines/ Antiobiotics / Bacteriology
Market Area: 
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