New research led by scientists at The Scripps Research Institute (TSRI), International AIDS Vaccine Initiative (IAVI) and The Rockefeller University shows that an experimental vaccine candidate can stimulate the immune system to block HIV infection in mice.
The new candidate has the potential to inform immunization strategies against AIDS for humans. The effort to develop a vaccine against HIV has so far struggled to elicit antibodies that can effectively fight off different strains of the fast and extensively mutating virus. The new results were published June 18 in concurrent studies in Cell and Science.
“The results are pretty spectacular,” said Dennis Burton, chair of the TSRI Department of Immunology and Microbial Science and scientific director of the IAVI Neutralizing Antibody Consortium (NAC) and National Institutes of Health Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery at TSRI.
The Science study was co-led by Burton; William Schief, TSRI Professor and IAVI NAC Director, Vaccine Design; and TSRI Professor David Nemazee. The Cell study was co-led by Schief and Michel Nussenzweig of The Rockefeller University.
The researchers’ long-term goal is to design a vaccine that prompts the body to produce antibodies that bind to HIV and prevent infection by many if not all of the virus’ variants. HIV mutates more rapidly into new strains than most other viruses and has an unprecedented ability to evade detection by the immune system. The researchers believe that a successful AIDS vaccine will need to consist of a series of related, but slightly different virus proteins (immunogens) to train the body to produce broadly neutralizing antibodies against HIV – a twist on traditional vaccination schemes, in which a person is exposed to the same immunogen multiple times.
In the new studies, the scientists tested an immunogen called eOD-GT8 60mer, a protein nanoparticle designed to mimic a critical part of the HIV envelope protein and to bind and activate B cells to produce antibodies 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 human-like antibodies.
The researchers showed that immunization with eOD-GT8 60mer produced antibody “precursors” with some of the traits necessary to recognize and block HIV infection, suggesting that eOD-GT8 60mer could be a good first step in a series of immunizations against HIV.
“The vaccine appears to work well in our mouse model to ‘prime’ the antibody response,” said Nemazee.
In the Cell paper, researchers used the same eOD-GT8 60mer immunogen but a slightly different mouse model.
“The immunogen proved capable of launching the mouse immune systems in the right direction. We look forward to the prospect of testing this exciting strategy in humans,” said Schief. The researchers are now investigating other immunogens that could work in conjunction with eOD-GT8 60mer.
A concurrent study also in Science, which included researchers from Amsterdam University, Weill Cornell Medical College, TSRI and IAVI, showed another engineered envelope-based immunogen triggered neutralizing antibody immune responses in rabbits and monkeys against a representative circulating strain of HIV and that, when presented in “native” form, the immunogen outperformed other “non-native” immunogens.
“Priming a broadly neutralizing antibody response to HIV-1 using a germline-targeting immunogen,” Dennis R. Burton, William R. Schief, David Nemazee, et al. Science
“Immunization for HIV-1 Broadly Neutralizing Antibodies in Human Ig Knock-In Mice,” William R. Schief, Michel C. Nussenzweig, et al. Cell
“HIV-1 Neutralizing Antibodies Induced by Native-like Envelope Trimers” Rogier W. Sanders, John P. Moore, et al. Science