Award winners
Winners 2009 have been awarded at the Meeting “5th Challenges in HIV-Infection – Advancing Patient Care”“ of August 27, 2009.
Interview with Alexandre Harari and Pierre-Alexandre Bart
Interview with Beda Joos and Huldrych Günthard
Alexandre Harari, PhD and Pierre-Alexandre Bart, MD, Centre Hospitalier Universitaire Vaudois, Division of Immunology and Allergy, have been assigned as one of two teams with the newly launched HIV Research Award 2009. Their study on T-cell responses induced by a DNA plus NYVAC vaccine regimen was rated best Swiss clinical study published within the last two years.
Mr Harari and Mr Bart, what are the findings of your study?
We have evaluated on 40 healthy HIV-seronegative volunteers the safety and immunogenicity of a prime-boost vaccine regimen comprising recombinant DNA and the poxvirus vector, NYVAC, both expressing HIV-1 immunogen. The results indicated that both DNA and NYVAC candidate vaccines are safe and well tolerated. Furthermore, vaccine-induced T-cell responses had characteristics of T-cell responses associated with control of HIV-1 infection, i.e. vigorous, polyfunctional, broad and durable. These results are very encouraging and they support the further clinical development of the DNA + NYVAC vaccine regimen. Furthermore, this study confirms the key role of Switzerland in the vaccine research field.
How important is this outcome for HIV-patients?
We have performed a similar study on HIV-1-infected subjects and obtained very interesting results. However, the field of therapeutic HIV vaccine is more complex and requires careful examination. The most relevant outcome of the present study is definitively a major step in the development of a preventive HIV vaccine.
Does the fact that your study was selected as best Swiss clinical study from all submitted applications bear any personal relevance?
Besides the gratification and honour to be co-recipients of the prize, we can only underline the fact that such a study has been performed thanks to the involvement of dedicated volunteers, the work of a dozen of highly skilled collaborators and the outstanding leadership from Pr Giuseppe Pantaleo.
For which purpose would you like to use the award money of 50’000 CHF? Any research projects planned?
There are a lot of question marks and caveats in the understanding of protective mechanism of effective vaccines. This knowledge is important for the evaluation and characterization of vaccine candidates. The award money will enable us to initiate new research projects to address the issue of the mechanism of protection of historical effective vaccines such as yellow fever or polio, for instance.
Beda Joos, PhD, and Prof. Huldrych Günthard, MD, University Hospital Zurich, Division of Infectious Diseases and Hospital Epidemiology, are the second winner team of the Bristol-Myers Squibb Switzerland HIV Research Award. Their study on HIV rebounds of latently infected cells was selected as best Swiss contribution in basic research published within the last two years.
Mr Joos, what are the results of your study?
During antiretroviral therapy the concentration of HIV in blood plasma falls below the limit of detection of the available assays, however, when the treatment is stopped the virus quickly rebounds. We analyzed the genetic composition of a great number of individual virus particles isolated from patients before therapy, during structured interruptions and later on over several years after definitive treatment discontinuation. Our results revealed that the emerging virus populations did not evolve from actively proliferating HIV but rather descend from a small fraction of ancestral proviruses resting in the latent reservoir or possibly from a single infected cell. This effect was quite sustained i.e. after treatment was stopped it took on average 3 years until the diversity of genetically distinct viruses reached the extent from before therapy.
Is there any applied or scientific relevance in your findings?
What we have found is that there is no significant residual replication going on during the times when the patients are treated because otherwise we would have detected an evolution of the virus in the detailed phylogenies. This ensures that the treatment is really very effective in delaying the progression of HIV and, when taken correctly, will not lead to the emergence of drug resistance. The observed clonal expansion of HIV from a single provirus clade is clear evidence of a severe evolutionary bottleneck induced by therapy.
Which importance does the HIV Research Award attach to your scientific research?
The HIV Research Award is a fantastic recognition of our work in the past and will also greatly help us to continue our research. The current projects running in our laboratory are primarily financed by competitive research grants and therefore we appreciate this support very much.
What are your plans? How would you like to use the award money?
The high mutation rate of HIV, which leads to a huge genetic diversity, and the capability to hide in latently infected cells make it incredibly difficult to attack the virus by vaccines or new drugs. With the award money we will try to gain new insight into the evolution and pathogenesis of HIV, the biological characteristics of the latent reservoir as well as interactions between virus and the human immune system. The first question we work on is to explore whether specific factors have an impact on virus transmission and which evolutionary events are taking place very early after infection determine the subsequent progression.
| 
