Currently, the Scripps Research Institute has developed a new candidate AIDS vaccine that can effectively overcome the technical barriers of previous AIDS vaccines and stimulate powerful anti-HIV antibody responses in animal experiments.
This latest AIDS vaccine strategy, published in the Science Advances, is based on the HIV envelope protein Env. Env is a complex and deformable molecule that is difficult to produce in vaccines. Therefore, it is hard to achieve effective immunization of HIV. However, scientists at the Scripps Research Institute have found a simple way to stabilize the Env protein in its ideal shape, even suitable for a variety of HIV strains. This stable Env protein is mounted on virus-like particles and can simulate the entire virus.
Jiang Zhu, associate professor of integrated structure and computational biology at the Scripps Research Institute, said: “This new approach is a universal strategy for addressing the long-standing problems of AIDS vaccine design.” Env protein has been the focus of HIV vaccine research because it plays a role in HIV infection and is the most exposed viral structure in the infected host’s immune system. The strategy inoculates the entire Env protein or its subunits in the human body, thereby stimulating the production of Env protein-binding antibodies that can prevent HIV-infected host cells in future contact with the virus.
On HIV strains, tight Env protein trimers protrude from the viral membrane and exhibit completely different shapes before and after infection of the cells. However, researchers have yet to find a universal method to stabilize Env trimers in the ideal pre-infected morphological structure.
At present, Jiang Zhu and the research team have modified the Env proteins of 30 to 40 different HIV strains, which have played a huge role in most cases. Then they further optimized the vaccine strategy by linking stable Env trimers (up to 60 at a time) to individual nanoparticles that mimic the globular structure of the entire virus. In this way, although the vaccine molecule is synthetic and lacks the genetic material of viral replication, it is very similar to a real invading virus for the immune system and can stimulate a stronger immune response. In laboratory tests, antibodies derived from Env vaccine samples found in the mice successfully neutralized a naturally transmitted HIV strain, and previous vaccine candidates were often unable to resist this HIV strain.