VAX May 2018
An e-newsletter presenting news and perspectives on HIV vaccine research...
HIV Vaccine Awareness Day (HVAD) began in 1998 to commemorate U.S. President Bill Clinton’s declaration on May 18, 1997: “Only a truly effective, preventive HIV vaccine can limit and eventually eliminate the threat of AIDS.”
Twenty years later, the U.S. government continues to lead the world in the search for an HIV vaccine. In an HVAD blog from the U.S. Agency for International Development (USAID), Margaret McCluskey, senior technical advisor for HIV Vaccine Research in the USAID Office of HIV/AIDS (OHA), discusses the American government’s central role in HIV vaccine research and development globally.
Visit our HVAD site to learn more.
Sustained investment is needed to support continued innovation in HIV vaccines. On HVAD 2018, IAVI is pleased to announce renewed funding from the Ministry of Foreign Affairs of Denmark through 2021.
“IAVI is grateful to the Danish government for its renewed investment in the development of an HIV vaccine, and for its continuing attention to the needs of communities disproportionally affected by the disease,” said Dr. Mark Feinberg, MD, PhD, President and CEO of IAVI. “We applaud the Ministry’s sustained commitment to combating HIV/AIDS, and we are proud to count the people of Denmark among our partners toward expediting the development of an effective HIV vaccine, and ultimately, achieving the goal of a world without AIDS.”
Read the press release.
After more than 15 years of concerted effort to design new and improved HIV vaccine candidates, two are poised to enter human clinical trials this year. These candidates are designed to induce potent and powerful antibodies against HIV, referred to as broadly neutralizing antibodies. They are the result of an extensive effort by scientists in IAVI’s Neutralizing Antibody Consortium and other institutions to decode how the immune system interacts with the virus and are among the first rationally designed HIV vaccine candidates to ever be tested in clinical trials.
Two developments led to this point. The first was the identification of dozens of broadly neutralizing HIV-specific antibodies. Starting with cohorts of thousands of HIV-infected individuals, IAVI and its global network of partners, as well as other groups were able to isolate scores of broadly neutralizing antibodies from chronically HIV-infected individuals. Isolation of these broadly neutralizing antibodies set off a new era of HIV vaccine development. By analyzing how these antibodies interact with the virus, scientists pinpointed several spots of vulnerability on HIV. They then used this information to rationally design a new generation of vaccine candidates.
The other development was obtaining a clearer understanding of the structure of HIV’s outermost protein known as Envelope, which is the target of all antibodies. For decades scientists were hindered by their inability to capture a crystal structure of this notoriously unstable protein, but recent advances have allowed them to both stabilize and understand the HIV Envelope protein in unprecedented detail.
One of the vaccine candidates about to enter clinical trials is an engineered protein that mimics one of the sites on HIV that is the target of broadly neutralizing antibodies. William Schief, a professor in the immunology and microbiology department at The Scripps Research Institute (TSRI) and director for vaccine design at IAVI’s Neutralizing Antibody Center at TSRI, and colleagues developed this immunogen using the latest technologies in protein engineering and computational design.
Preclinical studies of a nanoparticle based on this engineered protein, called eOD-GT8 60mer, indicated it was safe and could induce antibodies with the potential to develop into the types of broadly neutralizing antibodies that occur only rarely in HIV-infected people. It turns out that broadly neutralizing antibodies to HIV are highly specialized, and the immune system must undergo a multi-step process to make them.
Clinical evaluation of the eOD-GT8 60mer nanoparticle immunogen is slated to start in June. The vaccine will be administered in combination with an adjuvant to enhance immune responses. Adjuvants are biologic substances commonly used in vaccines to encourage a stronger and longer lasting immune response. While this protein is unlikely to elicit broadly neutralizing antibodies on its own, it is an important first step in understanding how to initiate and guide the production of these antibodies through vaccination.
For the first time, researchers are now also developing trimeric proteins that closely mimic the natural structure of the HIV Envelope protein and testing them as vaccine immunogens. After almost two decades of failed attempts to stabilize HIV’s floppy Envelope protein, John Moore, professor of microbiology and immunology at Weill Cornell Medical College, and colleagues developed one of these trimeric proteins – BG505 SOSIP.664 gp140. This protein will now be tested in combination with an adjuvant in clinical trials expected to start later this year.
These trials are two significant steps toward understanding how to induce broadly neutralizing antibodies through vaccination, which researchers widely agree will be necessary to provide immunity against HIV. Developing a vaccine remains the indispensable goal for ultimately ending AIDS.
Listen to a new podcast with Dr. Mark Feinberg, MD, PhD, President and CEO of IAVI. Find out why he thinks this is a very promising moment in the history of HIV vaccine research and hear him describe how some of the most sophisticated and insightful vaccine science ever done is driving the development of new vaccine approaches. Listen to the podcast here.