On
January 29, Public Assistance - Hospitals of Marseille (AP-HM) announced
the start of clinical trials of a therapeutic vaccine against HIV.
Embodying the work of Dr. Erwann Loret, these tests will be supervised
by Dr. Isabelle Ravaux, Service of Infectious Diseases, Hospital of the
Conception (AP-HM). It retails for around Doctissimo hopes this vaccine cure "Tat Oyi".
Doctissimo: What is the principle of the vaccine that you test?
Dr Isabelle Ravaux: It has been observed in people infected with HIV the presence of Tat protein produced by HIV. This protein is involved in the mechanisms of virus replication but also in extracellular "tricking" the immune system. It will firstly prevent killer cells to launch an attack HIV and secondly, it acts on B cells by reducing the production of antibodies against HIV.
Neutralizing Tat protein in an infected person, it hopes to restore his immunity and block the development of the disease. For this, we need to trigger the production of anti-Tat antibodies sufficient.
Doctissimo: How to successfully induce the immune response?
Dr Isabelle Ravaux: The choice of candidate is the brainchild of Erwann Loret, CNRS researcher. In a cohort of African patients who did not develop the disease (patients called HIV controllers ), in 1996 he discovered that the only abnormality was the virus called the Tat Oyi. In these patients, it was not functional and offered some protection to patients vis-à-vis HIV.
The idea of using this protein "Tat Oty" as a vaccine candidate has naturally imposed. The same team has succeeded in synthesizing this protein. The vaccine "Tat Oty" demonstrated in experiments in vitro and in vivo animal (including macaques) good efficiency, the results of which have been published in leading scientific journals. The next step is testing in humans, for which we received the green light from the National Safety of Medicines (MSNA) January 24, 2013.
Doctissimo: How will unfold clinical trials for this vaccine?
Dr Isabelle Ravaux: Clinical trials will take place in clinical investigation center (CIC) plurithematic 9502 AP-HM. Our biomedical research protocol EVA TAT is divided into two phases.
In a first time, 48 patients treated with HAART with undetectable viral load will be divided into 4 groups. Three receive a dose Tat Oyi different for each group. The latter will receive a placebo. The vaccination consists of three intradermal injections one month apart (on the surface of the skin without penetrating the muscle tissue or vascular). Treatment should be stopped two months to assess the time during which the viral load remains undetectable in patients. Patient recruitment began in February 2013. These Phase I / IIa aim to validate the principle of such a vaccination (it lead to the production of anti-TAT?) Check the safety of these injections transdermal humans and validate the optimal dose, which induces better immune response. The results of this phase will be conducted in December 2013.
If successful (lengthening the time control statistically significant viral load without treatment), 80 patients will be recruited from January 2014 to phase IIb, which will demonstrate the effectiveness of the vaccine. Half of the patients receive the optimal dose of the vaccine and the other half a placebo. The results will be analyzed in March 2015 and should be published around June 2015.
All these tests are "double-blind", that is to say that neither the prescriber nor the patient knows whether the used syringe containing vaccine or placebo (this is the method to ensure results tests by removing the psychological effects of the injection).
Doctissimo: What are the benefits for this therapeutic vaccine?
Dr Isabelle Ravaux: The first potential benefit of this vaccine would be to replace the triple therapy is not without side effects ... or at least be able to do without for a while.
You know you will have difficulty disposing of new classes of antiretroviral drugs in 20 years - it improves the comfort of taking the treatment, reducing the number of tablets including, but laboratories are investing less in AIDS research. It is therefore important to find new strategies to defeat HIV can develop resistance to treatment.
Tomorrow, a combination vaccine could take over the triple and perhaps act on the virus reservoirs (those places where the virus is immune to existing treatments).
Doctissimo: After years of false hopes, vaccines (especially therapeutic vaccines) seem to know a new impetus. Why is this?
Dr Isabelle Ravaux: Therapeutic vaccines aim to stimulate or today "educate" the immune system to fight against HIV. Strategy is no longer targeting surface proteins of the virus, which we now know they are too changeable to induce an effective immune response. The recent encouraging results on therapeutic vaccines explore this route, as the only case of a patient known cure HIV . For this, we need to find the "trick" as held by the two types of HIV virus - HIV-1 and HIV-2 - the target that will not easily mutate. The objective is to obtain an effective immune response and durable. It is our hope with the Tat protein.
Doctissimo: How was funded research?
Dr Isabelle Ravaux: The phases of basic research has been funded by the National Research Agency against AIDS (ANRS). A research protocol was then filed with the agency, which was not accepted as a priority.
To fund this research, it was therefore necessary to conduct a fundraiser, it is for this purpose that the biotechnology company BIOSANTECH was created. It is therefore of private funds but this research would not have been possible without the support of public actors: the University of Aix-Marseille and the CNRS have allowed Dr. Loret continue its research and Assistance Public - Hospitals of Marseille and the South East SATT allowing the conduct of clinical trials.
Dr Isabelle Ravaux: It has been observed in people infected with HIV the presence of Tat protein produced by HIV. This protein is involved in the mechanisms of virus replication but also in extracellular "tricking" the immune system. It will firstly prevent killer cells to launch an attack HIV and secondly, it acts on B cells by reducing the production of antibodies against HIV.
Neutralizing Tat protein in an infected person, it hopes to restore his immunity and block the development of the disease. For this, we need to trigger the production of anti-Tat antibodies sufficient.
Doctissimo: How to successfully induce the immune response?
Dr Isabelle Ravaux: The choice of candidate is the brainchild of Erwann Loret, CNRS researcher. In a cohort of African patients who did not develop the disease (patients called HIV controllers ), in 1996 he discovered that the only abnormality was the virus called the Tat Oyi. In these patients, it was not functional and offered some protection to patients vis-à-vis HIV.
The idea of using this protein "Tat Oty" as a vaccine candidate has naturally imposed. The same team has succeeded in synthesizing this protein. The vaccine "Tat Oty" demonstrated in experiments in vitro and in vivo animal (including macaques) good efficiency, the results of which have been published in leading scientific journals. The next step is testing in humans, for which we received the green light from the National Safety of Medicines (MSNA) January 24, 2013.
Doctissimo: How will unfold clinical trials for this vaccine?
Dr Isabelle Ravaux: Clinical trials will take place in clinical investigation center (CIC) plurithematic 9502 AP-HM. Our biomedical research protocol EVA TAT is divided into two phases.
In a first time, 48 patients treated with HAART with undetectable viral load will be divided into 4 groups. Three receive a dose Tat Oyi different for each group. The latter will receive a placebo. The vaccination consists of three intradermal injections one month apart (on the surface of the skin without penetrating the muscle tissue or vascular). Treatment should be stopped two months to assess the time during which the viral load remains undetectable in patients. Patient recruitment began in February 2013. These Phase I / IIa aim to validate the principle of such a vaccination (it lead to the production of anti-TAT?) Check the safety of these injections transdermal humans and validate the optimal dose, which induces better immune response. The results of this phase will be conducted in December 2013.
If successful (lengthening the time control statistically significant viral load without treatment), 80 patients will be recruited from January 2014 to phase IIb, which will demonstrate the effectiveness of the vaccine. Half of the patients receive the optimal dose of the vaccine and the other half a placebo. The results will be analyzed in March 2015 and should be published around June 2015.
All these tests are "double-blind", that is to say that neither the prescriber nor the patient knows whether the used syringe containing vaccine or placebo (this is the method to ensure results tests by removing the psychological effects of the injection).
Doctissimo: What are the benefits for this therapeutic vaccine?
Dr Isabelle Ravaux: The first potential benefit of this vaccine would be to replace the triple therapy is not without side effects ... or at least be able to do without for a while.
You know you will have difficulty disposing of new classes of antiretroviral drugs in 20 years - it improves the comfort of taking the treatment, reducing the number of tablets including, but laboratories are investing less in AIDS research. It is therefore important to find new strategies to defeat HIV can develop resistance to treatment.
Tomorrow, a combination vaccine could take over the triple and perhaps act on the virus reservoirs (those places where the virus is immune to existing treatments).
Doctissimo: After years of false hopes, vaccines (especially therapeutic vaccines) seem to know a new impetus. Why is this?
Dr Isabelle Ravaux: Therapeutic vaccines aim to stimulate or today "educate" the immune system to fight against HIV. Strategy is no longer targeting surface proteins of the virus, which we now know they are too changeable to induce an effective immune response. The recent encouraging results on therapeutic vaccines explore this route, as the only case of a patient known cure HIV . For this, we need to find the "trick" as held by the two types of HIV virus - HIV-1 and HIV-2 - the target that will not easily mutate. The objective is to obtain an effective immune response and durable. It is our hope with the Tat protein.
Doctissimo: How was funded research?
Dr Isabelle Ravaux: The phases of basic research has been funded by the National Research Agency against AIDS (ANRS). A research protocol was then filed with the agency, which was not accepted as a priority.
To fund this research, it was therefore necessary to conduct a fundraiser, it is for this purpose that the biotechnology company BIOSANTECH was created. It is therefore of private funds but this research would not have been possible without the support of public actors: the University of Aix-Marseille and the CNRS have allowed Dr. Loret continue its research and Assistance Public - Hospitals of Marseille and the South East SATT allowing the conduct of clinical trials.
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