Prototype candidate and potential new method to help prevent infection via broadly neutralizing antibodies will be assessed for safety, tolerability, durability
NEW YORK – IAVI, the International AIDS Vaccine Initiative, today announced the start of a Phase I clinical trial in the U.K. examining a prototype candidate and a potential new method to prevent HIV infection.
Approximately 24 healthy volunteers will each receive an injection of a vector carrying genetic instructions for producing a broadly neutralizing antibody (bNAb) called PG9, which has been shown to neutralize the Human Immunodeficiency Virus (HIV) in vitro. The vector carrying the PG9 is derived from a common adeno-associated virus (AAV).
The study will investigate if the participants’ muscle cells can then produce PG9, at what levels, and for how long, and will evaluate the safety, tolerability, and durability of the AAV-PG9 candidate at escalating doses.
The year-long, blinded, randomized trial is being conducted at the University of Surrey Clinical Research Centre in Guildford, U.K. The IAVI Human Immunology Laboratory (HIL), Imperial College London will perform the related immunogenicity testing.
The IAVI-sponsored trial is a significant step toward obtaining proof-of-concept for a novel approach to HIV prevention, as researchers could get a preliminary indication of whether this technique can be used to produce bNAbs in humans that might be able to prevent HIV infection. If the prototype strategy is successful, additional candidates could be developed to induce production of multiple bNAbs.
The PG9 antibody was isolated by IAVI and partners in its Neutralizing Antibody Consortium (NAC) as part of Protocol G, a landmark study to identify monoclonal bNAbs from HIV-infected volunteers. The new Phase I study marks the first use in people of bNAbs identified through Protocol G, results of which were first published inScience in 2009.
The Phase I study (known as IAVI A003 / CHOP HVDDT 001) is currently supported by the Bill & Melinda Gates Foundation, the Ministry of Foreign Affairs of The Netherlands, and the United States Agency for International Development (USAID), which administers the U.S. foreign assistance program providing economic and humanitarian assistance in more than 120 countries worldwide. The AAV-PG9 candidate was developed by Philip R. Johnson, M.D., Chief Scientific Officer and Executive Vice President at The Children’s Hospital of Philadelphia, with long-term support for basic and product development research and manufacturing from the National Institute of Allergy & Infectious Diseases, part of the National Institutes of Health.
The International AIDS Vaccine Initiative (IAVI) is a global not-for-profit organization whose mission is to ensure the development of safe, effective, accessible, preventive HIV vaccines for use throughout the world. Founded in 1996, IAVI works with private companies, academics, and civil society partners in 25 countries to research, design, and develop AIDS vaccine candidates. In addition, IAVI conducts policy analyses and serves as an advocate for the AIDS vaccine field. IAVI supports a comprehensive approach to addressing HIV and AIDS that balances the expansion and strengthening of existing HIV-prevention and treatment programs with targeted investments in the design and development of new tools to prevent HIV. IAVI is dedicated to ensuring that a future AIDS vaccine will be available and accessible to all who need it. IAVI’s work is made possible by generous support from many donors including: the Bill & Melinda Gates Foundation; the Ministry of Foreign Affairs of Denmark; Irish Aid; the Ministry of Finance of Japan; the Ministry of Foreign Affairs of the Netherlands; the Norwegian Agency for Development Cooperation (NORAD); the United Kingdom Department for International Development (DFID), and the United States Agency for International Development (USAID). The full list of IAVI donors is available at www.iavi.org.
IAVI launched the Neutralizing Antibody Consortium (NAC) in 2002 to solve one of the greatest challenges of AIDS vaccine development: the elicitation of broadly neutralizing antibodies (bNAbs) against HIV through vaccination. From the outset, the NAC focused on elucidating the molecular structures of a handful of broadly neutralizing anti-HIV antibodies isolated at the time in the hope of reverse engineering vaccines on the basis of what was learned about their interactions with HIV. Since 2009, thanks in large measure to the efforts of the NAC and a global search it launched for potent antibodies against HIV, more than two dozen bNAbs have been isolated from HIV-infected volunteers around the world. The structures of some of the most potent of these antibodies and their targets have also been solved. These discoveries are now being applied to the design of novel AIDS vaccine candidates.
In 2006, IAVI and the NAC launched Protocol G, a project to search for broadly neutralizing antibodies (bNAbs) against HIV, enlisting our clinical research partners in Africa, India, Thailand, Australia, the United Kingdom, and the United States. More than 1,800 healthy HIV-positive volunteers contributed blood samples to be screened. In 2009, scientists from IAVI, The Scripps Research Institute and Theraclone Sciences collaborated to isolate and characterize PG9 and PG16, the first new bNAbs to HIV seen in a decade and the first to be isolated from donors in developing countries, where the majority of new HIV infections occur. To date, more than 25 new bNAbs have been isolated and characterized from Protocol G specimens and many have been shared with researchers across the AIDS vaccine R&D field.