Darrell Irvine, PhD, Ragon Steering Committee Member and MIT Professor of Materials Science and Biological Engineering, has just published a paper in Nature Medicine showing a way to engineer an increased immune response to the vaccine adjuvant aluminum hydroxide, also known as alum, in an HIV vaccine given to animals.
Adjuvants like alum are used to heighten the body’s response to antigens, the vaccine component that trains the immune system to recognize an infectious disease. This heightened response increases the immune system’s “memory” of the antigen, allowing the body to more quickly recognize and attack the disease the antigen comes from. In most vaccines, alum and the antigen are given together; however, they can quickly separate once in the body. This means alum’s immune-enhancing effects are not always optimal during the vaccination process.
Here, Irvine and collaborators show that adding a molecule called phosphoserine to an HIV antigen allows the alum and antigen to bind together during vaccination. This keeps the antigen attached to alum during the entire immune response, which in turn greatly increases the immune response to the antigen. This results in increased production of HIV antibodies, which strengthens immune memory. Antibodies are the tools used by the immune system to recognize previously encountered diseases and initiate immune response. More antibodies in response to a vaccine means better protection.
However, HIV vaccines face special challenges. In response to HIV immunization, most of the antibodies made are binding antibodies. These antibodies bind to a site, or epitope, on HIV that is constantly mutating, and this initiates the immune response. As the virus mutates, the epitope changes and the antibody can no longer recognize it. Because HIV constantly mutates in the body, these antibodies become quickly outdated. Neutralizing antibodies (NAb) are antibodies that bind to an epitope which prevents the HIV virus from infecting a cell; they also initiate the immune response.
