The molecular and cellular biology of HIV is the subject of a range of basic research initiatives underway at ADARC. Our scientists have made seminal contributions to the understanding of HIV’s structure and the dynamics of viral replication. ADARC-led insights into how the immune system interferes with the virus’ life cycle are providing scientists a new basis for optimism about harnessing the body’s natural defenses to combat HIV. A current study is examining how evolution has endowed humans with resistance to most retroviruses, in hopes of discovering how they were extinguished and why HIV has gained resistance to our genomic defenses. In a study published two years ago, ADARC scientists identified tetherin, a protein on the surface of human cells that prevents mutant strains of HIV from spreading. As traditional research funding becomes more competitive and risk-averse, ADARC is sustaining a culture of discovery that prizes innovation and blue-sky inquiry.
With its clever mechanisms to dismantle and evade the immune system, HIV is a particularly difficult foe. Life-saving antiretroviral combination therapy championed by ADARC a decade ago has been improved and augmented by a new generation of medications: today there are over 25 drugs for treatment of HIV and AIDS, with more in the development pipeline. But the prospects for newly-infected patients – 40 years of treatment with difficult life choices and an uncertain outcome - are still unsatisfactory.
Today ADARC is pioneering new approaches to drug development through diverse research initiatives with a singular mission: to develop a finite course of treatment leading to HIV remission, and ultimately a cure. By probing the pathogenesis of HIV, ADARC scientists are gaining new insights that will enable patients to live longer, better lives.
HIV Prevention : Vaccine Development
ADARC scientists have engineered several candidate vaccines, which have been advanced into clinical testing in healthy HIV-negative volunteers. The vaccines target the Clade C strain of HIV that accounts for the most infections worldwide. Initial clinical trials demonstrated safety, and gave indications the candidate vaccines could stimulate specific immunity against the virus.
While these two vaccine candidates progress in development, funding from the Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery has enabled us to develop the "next generation" of HIV vaccines. We are developing novel vaccines and adjuvants that harness the dendritic cell to improve both the quantity and the quality of the immune response.
We are also utilizing novel vaccine delivery strategies to strengthen the immune response to DNA-based vaccines. The electroporation system has been shown to enhance the humoral and cellular immune response to several DNA-based vaccines in animals. The first Phase I clinical trial of this vaccine delivery method in healthy volunteers was successfully conducted by ADARC clinical investigators at The Rockefeller University Hospital.
HIV Prevention : Passive Administration of Neutralizing Antibodies & Microbicides
Scientists in our institute are also pursuing the use of a monoclonal antibodies directed to domain-2 of CD4 to block HIV infection. One such antibody, known as ibalizumab, has already shown antiviral effect in HIV-infected humans and SIV-infected monkeys. Ibalizumab is being tested for its ability to prevent SIV infection in monkeys and for its safety and tolerability in health human volunteers. Ultimately, the goal is to examine its utility in preventing HIV infection in humans. In addition, ADARC scientists are working to generate improved versions of ibalizumab so that the monoclonal antibody could be administered at a lower dose less frequently.
Moreover, our scientists are creating fusion monoclonal antibodies that are capable of inhibiting multiple steps/sites during HIV entry into a cell. Such engineered biologic molecules could be applicable to HV therapy as well.
ADARC is a leader in exploring new strategies for preventing HIV transmission. Faculty are exploring the scientific and practical application of microbicides—topical products that help prevent sexually transmitted diseases including HIV—that act as a physical barrier and/or killing the virus when used before intercourse. Microbicides have the potential to revolutionize HIV prevention by giving women the power to protect themselves.