The development of an effective HIV vaccine poses more challenges than most other efforts as the virus constantly mutates and conceals itself to avoid the defense of the immune system. Scientists at the International AIDS Vaccine Initiative (IAVI) and the Scripps Research Institute have discovered viral changes and antibody features that may demonstrate a design for a vaccine that targets those issues.
Years following the onset of an HIV infection, some may self-produce powerful broadly neutralizing antibodies (bnAbs) that could stop HIV from infecting immune cells. Although this process happens after infections, understanding it can guide a vaccine and it is the basis behind the study by Elise Landais, Ph.D., a senior research scientist with IAVI,
“HIV mutates 1000 times more than influenza, if not more. With HIV, even within one individual, you have an amazing diversity of strains,” Landais said in an interview. “We see how difficult it is to develop a flu vaccine that targets the correct strain for that year, let alone one that can cover all strains,” Landais explained that the other challenge is what is called the glycan shield, which could hide virus target areas from HIV antibodies and the shield is immunosilent, which means one’s immune system is unable to decipher it from sugars on our own proteins.
Landais’ team examined nearly 600 patients with HIV infection enrolled in the study and researchers discovered a patient that developed bnAbs targeting the V2 apex site on HIV’s surface. The V2 apex is a recently identified “site of vulnerability” where bnAbs can work most efficiently, blocking most HIV strains. Landais said, “We want to reproduce this process with a vaccine but to do it quicker than the human body, which takes years to develop bnAbs. To do so we need to understand how these exceptional antibodies ‘learned’ to deal with the HIV glycan shield and variability in these unique individuals”.
Using the technique dubbed next-generation sequencing, the researchers followed bnAb development back to its beginning stages and revealed that both viral variations and antibody structural features are critical for V2 apex bnAb development. The viral features show similar findings to those in another study’s patient that developed the same type of V2 apex bnAb responses.
Landais believes that these new findings “could offer a possible template for vaccine design,” but also recognizes more data is required to paint a clearer picture. The first step will be a group of scientists led by William Schief, Ph.D., an HIV researcher at Scripps Research Institute, will try to design immunogens with this information that instruct the immune system to develop the same type of HIV bnAbs that target the V2 apex.