Scientists have discovered three previously unknown human antibodies that neutralize HIV, two of which target a broad range of HIV strains. The findings, reported online July 8 in two Science papers, add a level of encouragement to the AIDS vaccine research field.
Nearly everyone infected with HIV makes some antibodies to it. The newly identified antibodies are unique in their breadth of neutralizing activity. One in particular, called VRC01, displays potency and broad coverage across HIV strains, says Peter Kwong, a structural biologist at the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) in Bethesda, Md., who coauthored both new reports.
In the new studies, the NIH Vaccine Research Center tested blood samples from HIV-infected people around the globe for antibodies against nearly 200 strains of HIV to determine how many strains each patient could neutralize. The blood from donor 45 was found to have broadly neutralizing antibody, donor 45, and was used to prepare monoclonal antibodies. The monoclonal antibodies were identified by screening 25 million of donor 45's antibody producing cells for production of broadly neutralizing antibodies specific for HIV envelope proteins. The screen identified three antibody producing cells with the desired activity: VRC01 and VRC02 neutralized 91 percent of HIV strains, and VRC03, neutralized 57 percent. These findings, and those of another group which were previously published over the past year establish a proof of the principle that it is possible for the human body to generate broadly neutralizing antibodies. However, and as noted by the authors of the reports, the design of a vaccine that can induce antibodies with similar specificity will require significantly more effort.
GeoVax is developing a vaccine that presents the natural form of HIV envelope proteins to the immune system on virus-like particles with the envelope proteins present in clusters of three, a confirmation known as trimers. GeoVax vaccines direct cells in the body of vaccinated persons to produce these virus-like particles. "This unique design presents the HIV envelope proteins to the immune system in forms that are very authentic. The antibody responses we've measured in our protection studies in non-human primates support the view that antibodies to the trimeric envelope proteins contribute to protection from infection" noted Harriet Robinson, Chief Scientific Officer of GeoVax.
""Antibodies induced by the GeoVax vaccine function not only through virus neutralization but also by binding directly to HIV viruses or infected cells and directing other types of immune responses that kill or reduce virus replication." added Dr. Robinson
Currently, GeoVax's preventative HIV vaccine candidate has completed Phase 1 clinical trials in humans, and is currently in a Phase 2 clinical trial being conducted by the HIV Vaccine Trials Network (HVTN). and sponsored by the Division of AIDS, NIAID, NIH This trial was initiated in January 2009 and will involve 300 participants at sites in the United States and South America. Based on current patient enrollment rates, the Company expects the trial to be completed during 2011.
Its therapeutic vaccine candidate has recently been allowed by the US Food and Drug Administration to begin a Phase 1 clinical trial. The vaccine candidate is intended as a treatment for individuals infected with HIV. Local Institutional Review Board approval has also been obtained. The trial's criteria will involve recently HIV-infected individuals who started drug treatment during their first year of infection.
In addition to these activities with its vaccine candidates, GeoVax is conducting preclinical research to assess the impact of incorporating an adjuvant (immune system stimulant) to its vaccines as next generation vaccine candidates. This work is being funded by the NIH through an Integrated Preclinical / Clinical AIDS Vaccine Development Grant (IPCAVD) to GeoVax.
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