HIV has the ability to evade detection by the human immune system and mutate rapidly into new strains, making traditional vaccine approaches that use a dead or inactive version of the virus ineffective. As a result, scientists have struggled to develop an effective vaccine for HIV for thirty years.
"The results are pretty spectacular," said Dennis Burton, chair of the TSRI Department of Immunology and Microbial Science and scientific director of two centers at TSRI, the IAVI Neutralizing Antibody Consortium (NAC) and the National Institutes of Health (NIH) Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID).
The study was co-led by Dr. Burton, TSRI Professor and IAVI NAC Director of Vaccine Design William Schief, and TSRI Professor David Nemazee. The Cell study was co-led by Dr. Schief and Michel Nussenzweig, who is Zanvil A. Cohn and Ralph M. Steinman Professor at The Rockefeller University and a Howard Hughes Medical Institute (HHMI) investigator.
The researchers' long-term goal is to design a vaccine that prompts the body to produce antibodies that bind to HIV and prevent infection.
The challenges in developing an HIV vaccine have led many researchers to believe that a successful AIDS vaccine will need to consist of a series of shots of related, but slightly different, proteins (immunogens) to train the body to produce broadly neutralizing antibodies that will work against nearly all strains of HIV – a twist on the traditional "booster" shot, in which a person is exposed to the same immunogen multiple times.
In the new studies, the scientists tested one of these potential proteins, an immunogen called eOD-GT8 60mer designed to bind and activate B cells needed to fight HIV. The eOD-GT8 60mer was developed in the Schief lab and tested in mouse models engineered by the Nemazee lab to produce antibodies that resemble human antibodies.
Using a technique called B cell sorting, the researchers showed that immunization with eOD-GT8 60mer produced antibody "precursors" with some of the traits necessary to recognize and block HIV infection. This suggested that eOD-GT8 60mer could be a good candidate to serve as the first in a series of immunizations against HIV.
"The vaccine appears to work well in our mouse model to 'prime' the antibody response," said Dr. Nemazee.
In the Cell paper, researchers used the same eOD-GT8 60mer immunogen but a slightly different mouse model. “The immunogen again launched the immune system in the right direction," said Dr. Schief.
A concurrent study also in Science, led by Professor John Moore of Weill Cornell Medical College, showed engineered immunogens also triggered immune responses in rabbit models and non-human primate models.
With eOD-GT8 60mer in the running as a potential contributor to an HIV vaccine, the researchers are now investigating other immunogens that could work in conjunction with it.
Dr. Schief said the Nemazee lab’s mouse models will be crucial resources for testing other engineered immunogens. He emphasized the importance of bringing different disciplines together to engineer mouse models, design antibodies and analyze results. "This was a beautiful collaboration of three labs at TSRI," he said.