Researchers Find Potential Map to More Effective HIV Vaccine
Apr. 3, 2013 - DURHAM, NC - By tracking the very earliest days of one person's robust immune response to HIV, researchers
have charted a new route for developing a long-sought vaccine that could boost the body's ability to neutralize the virus.
The research team, led by Barton F. Haynes, M.D., director of the Duke Human Vaccine Institute, and John Mascola,
M.D., acting director of the NIH Vaccine Research Center, have for the first time described the co-evolution of antibodies and
virus in a person with HIV whose immune system mounted a broad attack against the pathogen. Findings are published April 3,
2013, in the journal Nature.
Most vaccines work by inducing this antibody response, but the HIV virus has proved to be a difficult vaccine target.
When HIV antibodies are produced, they typically have a limited range, and the virus changes rapidly to escape harm, leading to an
arms race that the virus usually wins.
The current research was aided by new technologies that can detect early infection and track the subsequent immune
response and virus evolution. It fills gaps in knowledge that have impeded development of an effective vaccine for a virus that
has killed more than 30 million people worldwide.
"This project could only have been carried out by a multidisciplinary team working closely together," said Haynes, who led the work
as a project of the Duke Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery (CHAVI-ID) consortium, which is funded by the
National Institute of Allergy and Infectious Diseases. "For the first time, we have mapped not only the evolutionary pathway of
the antibody, but also the evolutionary pathway of the virus, defining the sequence of events involved that induce the broadly
The key to this finding was a person in Africa whose HIV infection was detected so early that the virus had not yet mutated to avoid
the immune assault. The individual also exhibited a fortuitous trait that occurs in only about 20 percent of people infected with
HIV - an immune system that produces broadly neutralizing antibodies. These immune weapons attack vulnerable sites of the virus
that are conserved despite mutations. In identifying the early viral infection, the team found the outer envelope, the viral
surface glycoprotein, which triggered the start of the broadly neutralizing antibody development.
By tracking the precise virus and antibody pathways involved, the Duke CHAVI-ID and NIH teams now have a detailed road map for development
of a potential vaccine, which involves immunogens with an outer envelope specifically selected to stimulate the production of broadly
"The next step is to use that information to make sequential viral envelopes and test them as experimental vaccines," Haynes
said. "This is a process of discovery and we've come a long way with regard to understanding what the problem has been."
In addition to Haynes, study authors at Duke include lead author Hua-Xin Liao, plus Feng Gao, S. Munir Alam, Kevin Wiehe,
Garnett Kelsoe, Guang Yang, Shi-Mao Xia, David C. Montefiori, Robert Parks, Krissey E. Lloyd, Richard M. Scearce, Kelly A. Soderberg,
Yue Chen, Fangping Cai and Sheri Chen.
Additional authors include Rebecca Lynch, Tongqing Zhou, Jiang Zhu, Lawrence Shapiro, Mark K. Louder, Lillan M. Tran,
Stephanie Moquin, Xiulian Du, M. Gordon Joyce, Sanjay Srivatsan, Baoshan Zhang, Anqi Zheng, Peter D. Kwong and John R. Mascola from
the National Institute of Allergy and Infectious Diseases; Thomas B. Kepler from Boston University; Scott D. Boyd, Andrew Z. Fire
and Krishna M. Roskin from Stanford University; Chaim A. Schramm and Zhenhai Zhang from Columbia University; James C. Mullikin
and the NISC Comparative Sequencing Program at NIH; S. Gnanakaran, Peter Hraber and Bette T.M. Korber of Los Alamos National
Laboratory; Myron Cohen of the University of North Carolina; Gift Kamanga of UNC Project, Malawi; George M. Shaw and
Beatrice H. Hahn of the University of Pennsylvania.
The NIAID and National Institutes of Health provided funding for the research to the Center for HIV/AIDS Vaccine Immunology
(AI067854) and the Center for Vaccine Immunology-Immunogen Discovery (AI100645).
Rachel Bloch Harrison
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