New findings to help HIV scientists establish ‘template’ for potent antibodies
New data published today in Immunity further illuminate how some human beings generate powerful, HIV-blocking antibodies. Led by scientists at the International AIDS Vaccine Initiative (IAVI) and The Scripps Research Institute (TSRI), the results offer important insight into a potential AIDS vaccine design.
"Uncovering the process by which neutralizing antibodies develop is critical to HIV vaccine design," said Elise Landais, Senior Research Scientist with IAVI and lead author of the study. "A small fraction of people living with HIV can naturally produce exceptionally powerful and broad antibodies that could prevent HIV from infecting their immune cells, but not until several years post-infection – long after that protection can help them. But it is of enormous interest to vaccine researchers."
From samples out of IAVI's landmark Protocol C epidemiological study, Landais and team selected an African individual infected with HIV subtype-A. Known as PC64, this volunteer developed HIV broadly neutralizing antibodies (bnAbs) targeting the vulnerable V2-apex site on HIV's surface. This particular type of bnAb is among the most potent, or effective neutralizers of HIV. Their breadth allows them to block the majority of HIV strains.
Applying an advanced technique called next-generation sequencing, the researchers were able to watch these bnAbs develop in reverse. They first took a series of "snapshots" depicting the interplay of PC64's immune response with the volunteer's infecting virus over time. Then, using these images, they retraced bnAb development back to the initiation stage, observing that certain viral changes promoted antibody breadth. Follow-up experiments revealed evolutionary similarities between the virus in PC64 and another infecting a CAPRISA study volunteer who developed the same type of bnAbs. The authors also highlighted the impact of additional viral structural attributes.
"These new findings are consistent and complementary with previous work by IAVI and partners and together could offer a possible template for vaccine design," said Landais. "We're one step closer to a vaccine that would protect healthy people from HIV infection, but further research is needed to achieve an optimal design."
Landais et. al. support a sequential immunization strategy, one of several that scientists are collaboratively investigating at the IAVI Neutralizing Antibody Center (NAC) at TSRI. Using data from IAVI's partner network of clinical research centers in Africa and India, NAC scientists aim to translate laboratory findings into a workable vaccine and other long-acting HIV prevention.
"Development of new and more effective prevention is paramount to ending the HIV/AIDS epidemic," said IAVI CEO Mark Feinberg. "Of all the tools needed to curb new HIV infections, a vaccine is arguably the most cost-effective and transformative. We're unlikely to end AIDS without one."
Founded in 1996, the International AIDS Vaccine Initiative (IAVI) is a nonprofit organization working to accelerate development of broadly effective HIV vaccines accessible to all. IAVI works with partners in 25 countries to research, design, and develop promising vaccine candidates. We collaborate with governments, partner with pharmaceutical and biotech companies, universities, hospitals, and civil society organizations, and conduct and support research in North America, Europe, Africa, and India. We strengthen the expertise and infrastructure to fight HIV/AIDS in sub-Saharan Africa, the epicenter of today's epidemic. And we advocate for policies, financing, and environments that drive the fastest possible development of HIV vaccines. Our vision is a world without AIDS, and that world has a vaccine. 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 in partnership with The World Bank; 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 http://www.iavi.org.
About The Scripps Research Institute
The Scripps Research Institute (TSRI) is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs more than 2,500 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists–including two Nobel laureates and 20 members of the National Academies of Science, Engineering or Medicine–work toward their next discoveries. The institute's graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. In October 2016, TSRI announced a strategic affiliation with the California Institute for Biomedical Research (Calibr), representing a renewed commitment to the discovery and development of new medicines to address unmet medical needs. For more information, see http://www.scripps.edu.