Scientists test new vaccine-design approach on viruses
William Schief, the team leader, and his colleagues used the new technique to engineer an immunogen to reliably initiate an effective response against multiple types of HIV. The study, which was published in Science on Thursday, demonstrates a potential path to stimulating the immune system to produce a correct antibody response against a wide range of viral strains.
"We're hoping to test this immunogen soon in mice engineered to produce human antibodies, and eventually in humans," Schief said.
Researchers have identified multiple broadly neutralizing antibodies, but they have yet to elicit the production of the antibodies in the body through a vaccine.
"For example, to elicit broadly neutralizing antibodies called VRC01-class antibodies that neutralize 90 percent of known HIV strains, you could try using the HIV envelope protein as your immunogen, but you run into the problem that the envelope protein doesn't bind with any detectable affinity to the B cells needed to launch a broadly neutralizing antibody response," Schief said.
In an effort to initiate the VRC01-class antibody response, the researchers looked into a method for designing vaccine immunogens. The scientists used a protein modeling software suite called Rosetta to develop an artificial immunogen that would improve how well the antibodies bind to HIV's envelope protein. After identifying dozens of mutations that could improve the binding, generating libraries with millions of possible mutant antibodies and screening the candidates, the team developed an optimized immunogen called eOD-GT6.
After adapting the antibody to make it look like a virus using a virus-mimicking particle from copies of an obscure bacterial enzyme, eOD-GT6 effectively worked to activate VRC01 antibodies.
"Essentially it's a self-assembling nanoparticle that presents the immunogen in a properly oriented way," Sergey Menis, a visiting graduate student in Schief's laboratory, said. "We're hoping that this approach can be used not just for an HIV vaccine but for many other vaccines, too."
After the team tests the immunogen in lab animals, Schief said the hope is to test the approach in humans as soon as possible.
"it will be really important to find out if this works in a human being," Schief said.