Fred Hutch is a longtime leader in the global fight against HIV/AIDS. Our research on prevention, treatment and potential cures includes active studies and statistical assistance to studies in countries on five continents. We use our expertise in virology and immunology to investigate HIV at the molecular level, with the goal of identifying events that lead to infection and transmission and to understand the complex relationship between HIV and the immune system.
Fred Hutch scientists, biostatisticians and epidemiologists study the evolutionary history of HIV and track the course of the epidemic. We analyze the results of experimental vaccines and microbicides to prevent the disease. In addition to the design and oversight of HIV vaccine clinical trials at HVTN, our researchers study mechanisms of natural protection found in a small subset of people who can suppress the virus without medication. We also search for broadly neutralizing antibodies, rare proteins that could work against multiple strains of HIV. We are testing new vaccines designed to get immune cells to produce such antibodies reliably — the holy grail of HIV vaccine research. We continue to study new technologies with the goal of curing HIV in people who are already infected.
Most HIV/AIDS vaccines fail because the immune proteins, or antibodies, that they generate zero in on specific surface features of the virus that can rapidly change their shape through genetic mutation whenever the virus makes copies of itself. These mutations allow the virus to hide from antibodies.
But some antibodies, known as broadly neutralizing antibodies, are able to block many variants of a virus. We are designing vaccines that cause the body to make this type of antibody against HIV. They target parts of the HIV surface that cannot change shape without crippling the virus. In theory, the virus cannot evade such a vaccine. Tests will show if the vaccine works.
Through the defeatHIV program, we are testing ways to:
Our scientists are exploring how the microbiome — the vast community of bacteria and other foreign microbial life that inhabits our bodies — interacts with the immune system and may influence vaccine responses.
The failure of one experimental HIV vaccine may have been due to a “cross-reaction” with bacteria in the human gut. Components of the vaccine that were meant to trigger an immune response against HIV instead targeted a similar-looking feature on the cell membranes of common gut bacteria. The vaccine was apparently fooled, as if by a decoy, into reacting against the bacteria instead.
We are learning how protective antibody responses against HIV develop. For instance, infants can generate protective antibodies more quickly than adults. Work by our scientists suggests that the immune responses of infants hold insights that could help improve HIV vaccine design.
Our researchers are also studying how HIV slips past our immune system. Using a cutting-edge approach called deep mutational scanning, our scientists have compiled a library of every possible genetic mutation that affects the proteins on the surface of HIV. Their tests are showing how the structure of each mutation affects the ability of HIV to escape antibodies. This information can help us design a more effective vaccine.
Researchers led by Dr. Julie McElrath are investigating why about 1 percent of people who are living with HIV can naturally suppress HIV without medication. The goal is to find out if these “long-term nonprogressors,” or “elite controllers,” carry unknown biological mechanisms that protect them from HIV. If researchers can duplicate these mechanisms, they may be able to prevent HIV progression and improve outcomes among a much broader group of people with HIV. The studies are based at the Seattle Vaccine Trials Unit, one of more than 40 HVTN research sites around the world.
When Bill Hall tested positive for HIV in 1986, he assumed it was a death sentence. The next 10 years were a blur of visiting friends in the hospital and going to funerals. Then he began taking an antiretroviral cocktail that kept the virus in check. He survived. But in 2007, he had another shock: he was diagnosed with non-Hodgkin lymphoma. He continues to survive and says, “I’m actually doing quite well, considering.”