HIV/AIDS

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:

• Genetically engineer blood cells to be resistant to HIV replication
• Develop gene therapy techniques that mutate HIV and render it incapable of replicating in an infected person
• Deliver synthetic proteins that stop HIV reactivation
• Stop the proliferation of cells that sustain the HIV reservoir

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.