Antibody-based HIV Prevention: Preparing for Success

Mark Feinberg, M.D., Ph.D., is President and CEO of IAVI.

By Mark Feinberg, M.D., Ph.D., President and CEO of IAVI

Among the topics being discussed at the biannual HIV Research for Prevention (R4P) conference now taking place in Madrid, antibodies are at the forefront. Researchers are discussing innovative approaches to induce protective antibodies against HIV by vaccination, as well as the potential for these antibodies to be used directly to prevent HIV infection.

Since 2009, when IAVI scientists and their partners were among the first to identify a new class of HIV-specific antibodies, hundreds of potent antibodies with the ability to neutralize a broad swath of HIV variants have been identified. These so-called broadly neutralizing antibodies (bNAbs) are now reinvigorating efforts to design vaccine immunogens. IAVI and its partners recently advanced one of these immunogens into clinical trials. This candidate was engineered using the latest tools of computational and structural biology by researchers at the IAVI Neutralizing Antibody Center at Scripps Research in La Jolla, California.

Several researchers, including those at IAVI, are also pursuing passive administration of bNAbs. The results of the first study evaluating the efficacy of one passively administered antibody for HIV prevention are expected within the next two years. Meanwhile, scientists are developing bNAbs with improved breadth, potency, and duration of action. IAVI and our scientific collaborators at the Institute for Protein Innovation (IPI) at Harvard University are applying new methods to optimize bNAbs. At R4P, Devin Sok, director of antibody discovery and development at IAVI, Joe Jardine, head of antibody discovery at IPI, and their collaborators will report on an enhanced version of one IAVI antibody, ePGT121, which has greatly improved potency and improved neutralization breadth compared to its parent antibody. These improvements show it is possible to make antibodies that are even more potent and broadly neutralizing than those that develop in response to natural HIV infection. Such innovation will help make antibody prophylaxis a more feasible and affordable approach.

Researchers are also advancing cocktails of different antibodies, as well as a tri-specific agent that combines portions of three antibodies into a single molecule, into clinical trials.

This is exciting work with great potential, but like everything in science, there is no guarantee it will work. Still, we must plan for success. Success in antibody prophylaxis is not just identifying the optimal combination of bNAbs that are most effective in blocking HIV infection. Success also requires making sure these bNAbs are made available promptly and are affordable and accessible across the globe, particularly in the places where HIV infection rates remain unacceptably high.

Making globally accessible and affordable antibody products a reality will require scientific innovation and creative partnerships. IAVI is committed to this as part of our overall antibody strategy. This is why we recently announced a collaboration with Serum Institute of India, the world’s largest vaccine producer, to develop and manufacture low-cost, antibody-based HIV products. This collaboration takes advantage of our complementary expertise and establishes a model for developing and implementing sustainable global health solutions. Working with Serum Institute, as well as other partners, we will forge a viable path to developing, testing, and if effective, expediting the delivery of antibody-based products. The goal of this partnership is to benefit the broad field of HIV prevention by enabling the most promising combination of antibodies to be developed.

The success in providing affordable, widespread access to life-saving antiretroviral therapy in low-income countries is a model for global access to antibody-based prevention. However, the production of monoclonal antibodies differs in several significant ways from methods to produce generic antiretroviral drugs. We will need both novel technologies and new business models to provide access to affordable bNAb combinations. If the HIV prevention community can achieve global access to bNAbs, it will create a pathway for providing wider access to monoclonal antibodies targeting other global health challenges as well.

There is no guarantee that these HIV-specific monoclonal antibodies will be efficacious, but if they are, it would be a tragedy if we are not prepared to act quickly and decisively to provide access to them in populations at high risk of HIV infection. The need for new ways to prevent HIV remains as strong as ever, and so must our commitment to delivering these methods to those most in need.