What types of anti-HIV-related clinical trials are being developed by the VRI?
The Vaccine Research Institute (VRI), in association with the ANRS, is selecting volunteers willing to participate in research on vaccines (preventive and therapeutic) against HIV.
The VRI is developing two types of clinical trials involving different types of volunteers.
- Clinical trials aimed at developing a preventive vaccine, and therefore involving healthy volunteers.
- Therapeutic vaccine clinical trials, conducted on patients already carrying HIV.
In 2015, one prophylactic clinical trial (ANRS VRI01) and one therapeutic (ANRS 149 LIGHT-VRI02) were conducted in healthy volunteers and HIV-infected individuals respectively (200 volunteers in total). The last vaccinations in both trials and the monitoring phase have been completed in 2016 and the results are currently under analysis. The knowledge that will be generated from these two trials will be decisive for the next VRI clinical development plan (prophylactic and therapeutic trials) that will be set up with the DC-targeting candidate vaccines elaborated by the VRI.
ANRS VRI01 prophylaxis trial (March 2014-March 2016)was a Phase I / II trial evaluating the immunogenicity and tolerance of 4 "prime-boost" combinations of HIV vaccine candidates (MVA HIV-B / LIPO-5; LIPO-5 / MVA HIV-B; GTU-MultiHIV B / LIPO-5; GTU-MultiHIV B / MVA HIV-B) in healthy volunteers at low risk of HIV infection. For this trial, the company FIT Biotech provided the doses of GTU-MultiHIV B and the ANRS the MVA-HIV-B and the LIPO-5.
ANRS 149 LIGHT-VRI02 therapeutic trial (July 2013-October 2016) was a Phase II evaluation of an immunization strategy combining a DNA vaccine (GTU-MultiHIV B) followed by a lipopeptide vaccine (LIPO-5 ) versus placebo, in the control of viral replication after stopping antiretrovirals in patients infected with HIV-1. For this trial, FIT Biotech provided doses of GTU-MultiHIV B and placebo and the ANRS the LIPO-5.
|Jean-Daniel LELIEVRE, head of VRI Division CLINICAL DEVELOPMENT and PI (or co-PI) of several clinical trials in the field of immune-based therapies of HIV or vaccinology|
The VRI is developing new promising vaccines, i.e. Dendritic Cells (DC)-targeting vaccines. Indeed, DCs are recognized as potent antigen-presenting cells that capture, process, present Ag to immune cells and deliver signals driving adaptive immunity. The conventional approach is to use a specific monoclonal antibody directed against a particular endocytic receptor to carry the antigen to the DCs, resulting in processing and presentation of antigenic peptide to T and B cells.
The VRI clinical development plan will thus focus on this new generation of vaccines. These DC-targeting vaccines will be associated with the most promising candidate vaccines selected in Phase I and II by the VRI and its collaborators, the therapeutic knowledge feeding the prophylactic program and vice versa.
In addition, association with immunotherapies is also a path that the VRI is investigating to improve the immune response against HIV. As such, an innovative therapeutic trial associating therapeutic vaccination with immunotherapy (Vedolizumab) is planned in 2018 within the frame of the consortium EHVA (European HIV Vaccine alliance www.ehv-a.eu).
These two trials included around 200 HIV infected individuals and healthy volunteers and allowed to define the best vaccine combination. Indeed, while GTU®-multiHIV + LIPO-5 combination was poorly immunogenic and showed therefore disappointing results in VRI02 where it was the only combination used, GTU®-multiHIV + MVA HIV-B combination revealed to be highly immunogenic in healthy volunteers (VRI01 trial) which allows to consider the extension of its clinical development (results presented at HIVR4P 2016, Chicago and IAS 2017, Paris, manuscripts in preparation).
In addition, despite the absence of effect on the viral control demonstrated with the vaccine combination tested in LIGHT, we will gain further knowledge on the understanding of correlates of protection and the viral reservoir. Indeed, via sampling of ~100 HIV-infected individuals we have generated a unique large set of immunological and virological data in France that will be submitted to deep analysis through big data and system vaccinology approach. This will generate crucial information for the next clinical trials to come.
These two clinical trials had as objectives to elaborate a prime/boost strategy using 3 different “classical” vaccines against HIV in healthy volunteers and HIV-infected individuals. Two of these vaccines are developed by the Inserm-ANRS: one pox vector vaccine, MVA-HIV-B, and one lipopetide vaccine, LIPO-5, and one DNA vaccine is developed by FIT Biotech, GTU-MultiHIVB. These vaccines encode shared homologous HIV sequences allowing to stimulate the immune system via different type of presentation of the same HIV peptides.
To see Prof. Jean-Daniel LELIEVRE biography, click here