First HIV vaccine trial conducted simultaneously in the U.S. and in Africa now underway
Seattle, WA - The HIV Vaccine Trials Network (HVTN) has launched an international clinical trial that will test a promising HIV prevention vaccine candidate in humans. The vaccine, called EP HIV-1090, will be tested in 42 volunteers in the U.S. and Botswana. This trial has the multiple distinctions of being the first trial to be conducted simultaneously in the U.S. and Africa, the first HVTN trial to take place in Africa, and the first HVTN trial to be conducted simultaneously in the U.S. and abroad.
“This trial marks a new stage in global HIV research,” stated Dr. Larry Corey, Principal Investigator for the HVTN. “Africa is carrying the greatest burden of the AIDS epidemic, and it is therefore crucial that HIV vaccine development include African leadership, participation and support.”
Previous human trials conducted by the HVTN outside the U.S. have always followed a trial performed in the U.S. This time participants will receive the same inoculations during the same time period in the Boston, Massachusetts area, in St. Louis, Missouri, and in Gaborone, Botswana.
“This study is a significant and hopeful step in Botswana’s battle against the scourge of AIDS,” said Joy Phumaphi, Botswana’s Minister of Health. “The volunteers for this trial exemplify the best of the traditional Botswana values of altruism and selflessness.”
The vaccine candidate is a multi-epitope vaccine developed by Epimmune, a San Diego, California based pharmaceutical company. EP HIV-1090 is assembled from synthetically produced DNA. These small pieces of DNA manufacture specific proteins like the ones in HIV. These proteins have elements referred to as epitopes, which in this case prepare the body to recognize real HIV. There is no way that any part of this vaccine candidate can cause HIV infection. As the body learns to mount a defense against the vaccine, the hope is that it will also learn to fight off real HIV, should the body ever be exposed to the actual virus.
The EP HIV-1090 trial is a Phase I trial, meaning that it is intended to test the safety and immunogenicity (effect on the immune system) of the vaccine candidate. The double-blinded trial will enroll 42 volunteers, 36 of whom will receive the candidate vaccine and six of whom will receive the placebo. Participants will be healthy, HIV-1-uninfected adults between the ages of 18 and 40. The trial will last 18 months, after which time the data will be evaluated. The candidate vaccine will then be considered for the next stage of testing.
Initial lab studies have shown that EP HIV-1090 may have the potential to induce an initial immune response against subtypes of HIV seen in the U.S. and in Africa. Testing the product in both countries in the same trial will allow for a more thorough understanding of the best way to proceed with this vaccine candidate.
“Our understanding of HIV vaccine science grows with each human trial we undertake,” says Max Essex, chairman of the Botswana-Harvard Partnership and Principal Investigator of the Botswana HIV Vaccine Trial Unit. “Vaccine development is a complicated process, and the HIV virus is particularly intricate. Clinical trials are crucial to building the body of knowledge we need to achieve an effective HIV vaccine.”
The HVTN is a global network of trial sites, linking scientists, community members, governments and industry in the effort to develop an HIV vaccine. The Network allows for the expedting of clinical trials of potential vaccines in a manner that respects the diversity of the communities involved in the research.
The HVTN currently has four sites in Africa: Gaborone, Botswana; Durban, South Africa and Soweto, South Africa; and Blantyre, Malawi. Additional HVTN trials are scheduled to begin soon in South Africa.
No live HIV virus was used in making the vaccine candidate, so there is no possible way for EP HIV-1090 to cause HIV infection in any participant.
ADDITIONAL VACCINE SCIENCE
This candidate vaccine is a DNA plasmid-type vaccine, in which the DNA plasmid functions as a base for the rest of the vaccine. Due to their small size, DNA plasmids are
easily manipulated, both to keep them from replicating and also to encode within them defined, specific genes. Their advantage as vectors is their ability to mimic intracellular pathogens, and therefore induce appropriate T-cell (immune system) responses. There are no known ways for the plasmid used to generate viral or oncogenic proteins, making plasmids reliably safe vectors.
In the vaccine candidate, EP HIV-1090, pieces of viral genes are inserted into the plasmid, from which the genes then produce specific proteins. In the case of this vaccine the pieces of viral genes are taken from the genes gag, pol, vpr, nef, rev, and env, which in turn produce proteins called epitopes. The epitopes function as docking machinery, to which immune cells, called CTL (cytotoxic T-lymphocyte) cells, attach. The immune system is stimulated to attack by the presence of the foreign DNA plasmid, and then learns to recognize the particular epitopes encoded within the plasmid vaccine. These epitopes closely resemble ones in live HIV, but without real HIV’s ability to be damaging. The hope is that if at a future time the body is then exposed to HIV through sexual behavior or drug use it will have learned how to combat it.
In this vaccine candidate, an additional proprietary universal helper T-cell epitope has
been added to enhance the magnitude and duration of the immune response. There is also
an adjuvant of PVP (polyvinylpyrrolidone) to facilitate dispersal of the vaccine through tissue, and to induce uptake into skin and muscle cells.
The hope with this vaccine candidate is that by incorporating multiple CTL epitopes into one vaccine it will increase the likelihood of generating an immune response in people with various genetic backgrounds. It may also invoke a broad range of CTL responses, thereby providing a vaccine response that is both directed and widespread. Data exist to support the hypothesis that increased HIV-specific CTL response can control and possibly eliminate the virus.
The 21 immunogenic epitopes included in this vaccine were identified using HLA transgenic mice. Additional animal studies indicated positive immunologic responses. These were followed by lab studies showing CTL responses to the epitopes in human lymphocytes, providing support for moving EP HIV-1090 into the initial human trial.
The trial is randomized, double-blinded and placebo-controlled, with an eighteen-month duration. The trial has a primary endpoint of safety and tolerability and a secondary endpoint of immunogenicity. Forty-two volunteers will be enrolled, 36 of whom will receive candidate vaccine and six of whom will receive the placebo. Three dosages will be tested, each with four injection schedules over a six-month period. Participants will be healthy, HIV-1-uninfected adults between the ages of 18 and 40 who have been tested and found to have certain HLA genetic types that might be optimal for this vaccine.
ABOUT THE HIV VACCINE TRIALS NETWORK
The HIV Vaccine Trials Network is a partnership of investigators, clinical trial sites, and community representatives working with industry and governments in the global search for a preventative HIV vaccine. Funded through the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) an agency of the Department of Health and Human Services, the Network conducts all phases of clinical trials, from evaluating candidate vaccines for safety and the ability to stimulate immune responses, to testing vaccine efficacy. Headquartered at the Fred Hutchinson Cancer Research Center in Seattle, Washington, the Network at present includes 25 research sites on four continents. For more information, please visit www.hvtn.org.
ABOUT THE CENTER FOR VACCINE DEVELOPMENT AT SAINT LOUIS UNIVERSITY
The Center for Vaccine Development at Saint Louis University is a multi-disciplinary research center designed to conduct basic and clinical research on new vaccines and biologics. For more information, please visit http://medschool.slu.edu/vaccine/.
ABOUT THE HIV VACCINE TRIALS UNIT AT HARVARD MEDICAL SCHOOL
The HIV Vaccine Trials Unit (HVTU) at Harvard Medical School is a research partnership that includes Fenway Community Health, Brigham and Women's Hospital
and Miriam Hospital, a teaching affiliate of Brown University Medical School. The
partnership conducts clinical trials in the search for a preventative HIV vaccine in collaboration with the HIV Vaccine Trials Network.
ABOUT THE BOTSWANA-HARVARD AIDS INSTITUTE PARTNERSHIP FOR HIV RESEARCH AND EDUCATION
The Botswana-Harvard AIDS Institute Partnership for HIV Research and Education is a collaborative research and training initiative between the Government of the Republic of Botswana and the Harvard AIDS Institute. The Botswana-Harvard AIDS Institute Partnership conducts epidemiological, laboratory-based and clinical research on the prevention and treatment of HIV-1C diseases. For more information, please visit http://www.bhp.org.bw.
ABOUT EPIMMUNE, INC.
Epimmune, Inc., based in San Diego, California, is focused on the development of pharmaceutical products using multiple epitopes to specifically activate the body’s immune system. The Company’s preventative drug candidates have been designed to protect against disease by teaching the body’s immune system to react quickly when exposed to infectious agents. For more information, please visit http://www.epimmune.com.
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*** FACT SHEET FOR HVTN 048 ***
THIS TRIAL IS A PHASE I TRIAL OF A MULTI-EPITOPE VACCINE, EP HIV-1090*, DEVELOPED BY EPIMMUNE, INC.
* The candidate vaccine is assembled from synthetically produced DNA, and incorporates small pieces of DNA, which manufacture specific proteins like the ones in HIV. These proteins have elements referred to as epitopes, which in this case prepare the body to recognize real HIV.
* This trial is to be conducted in HIV-1 uninfected volunteers. Phase I trials test vaccine candidates for safety and immunogenicity (the level of immune response).
* No live HIV is used in this vaccine candidate, so there is no possible way for volunteers to develop HIV from the vaccine.
THIS TRIAL WILL BE THE FIRST HVTN TRIAL CONDUCTED IN THE U.S. AND ABROAD SIMULTANEOUSLY, AND THE FIRST TRIAL EVER CONDUCTED SIMULTANEOUSLY IN THE U.S. AND AFRICA.
* The trial will be conducted at several sites in the Boston, Massachusetts area through the Harvard Medical School, in St. Louis, Missouri through the St. Louis University, and in Gaborone, Botswana through the Botswana-Harvard Partnership for HIV Research and Education.
* This is the HVTN’s first African trial. Additional HVTN trials are planned to begin soon in South Africa and Malawi.
* Although the entire trial will be carried out in the same time period, the first inoculations will be given in the U.S., and the trial will then proceed with continued enrollment in Botswana and the U.S.
THIS WILL BE A RANDOMIZED, DOUBLE-BLINDED, MULTI-CENTER, PLACEBO-CONTROLLED TRIAL WITH 42 PARTICIPANTS.
* Participants will be healthy, HIV-uninfected adults between the ages of 18 and 40.
* The trial will last 18 months, with the injections received over a six month course, followed by a year of observation.
* Participants will have 12 clinic visits, including four injection dates and 12 blood draws.
* The test will be double-blinded, meaning neither participants nor investigators will know who received the vaccine candidate and who received placebo. Thirty-six participants will get the vaccine candidate, and 6 will receive placebo.
* There will be three vaccine groups, with the vaccine candidate recipients of each group receiving different dosages. Participants will be assigned to these groups randomly.
* The safety of the trial will be monitored by several groups, including a Safety Monitoring Board that will include representatives from the host country.
THE TRIAL IS BEING CONDUCTED BY THE HIV VACCINE TRIALS NETWORK, A GLOBAL PARTNERSHIP THAT CONDUCTS INTERNATIONAL CLINICAL HIV VACCINE TRIALS.
* The Network links 25 sites worldwide, bringing together investigators, clinical trial sites and community representatives in the search for a preventative HIV vaccine.
* The HVTN is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH), within the Department of Health and Human Services.
* Partner institutions for this trial are the Harvard School of Public Health, the Botswana-Harvard Partnership for HIV Research and Education, Brown University, Brigham & Women’s Hospital, Fenway Community Health, and St. Louis University.
* Epimmune, Inc. is a San Diego, California based pharmaceutical company specializing in multi-epitope products.
(*) EP HIV-1090 is a DNA plasmid vaccine encoding 21 CTL epitopes of HIV-1 gag, pol, vpr, nef, rev, and env peptides. The vaccine also encodes the universal HTL epitope PADRE. The adjuvant is PVP, polyvinylpyrrolidone, excipient in sterile phosphate buffered saline (PBS).
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