Researchers believe a new molecule discovered could someday lead to a successful HIV vaccine.
A team from the University of Maryland (UMD) and Duke University has created a protein-sugar vaccine candidate in an animal model that has shown the ability to stimulate an immune response against the sugars that form a protective shield around HIV.
The researchers designed a vaccine candidate using an HIV protein fragment linked to a sugar group that, when injected into rabbits, stimulated the antibody responses against the sugar shield in four different HIV strains.
The protein fragment comes from gp120—a protein that covers HIV like a protective envelop, which is covered by a sugar shield that bolsters HIV’s defenses.
“An obstacle to creating an effective HIV vaccine is the difficulty of getting the immune system to generate antibodies against the sugar shield of multiple HIV strains,” Lai-Xi Wang, a professor of chemistry and biochemistry at UMD, said in a statement. “Our method addresses this problem by designing a vaccine component that mimics a protein-sugar part of this shield.”
Researchers have previously targeted gp120, but the sugar shield on HIV resembles sugars found in the human body and does not stimulate a strong immune response.
Also there are more than 60 strains of HIV that exist, with the virus being able to mutate frequently.
These researchers focused on a small fragment of the protein that is common among different HIV strains. They used a synthetic chemistry method to combine the gp120 fragment with a sugar molecule that is also shared among HIV strains.
They then injected the protein-sugar vaccine candidate into rabbits and found that the rabbits’ immune system produced antibodies that physically bound to gp120 that was present in four dominant strains of HIV.
When they injected rabbits with a vaccine candidate that contained the protein fragment without the sugar group, they found that the antibodies bound to gp120 were from only one HIV strain.
“This result was significant because producing antibodies that directly target the defensive sugar shield is an important step in developing immunity against the target and therefore the first step in developing a truly effective vaccine,” Wang said.
While the rabbits’ antibodies bound to gp120, they did not prevent live HIV from injecting cells.
“We have not hit a home run yet,” Wang said. “But the ability of the vaccine candidate to raise substantial antibodies against the sugar shield in only two months is encouraging; other studies took up to four years to achieve similar results.
“This means that our molecule is a relatively strong inducer of the immune response,” he added.
The researchers will now conduct longer-term studies in combination with other vaccine candidates to hone in on the specific areas of gp120 the antibodies are binding to and determine how they can increase the antibodies’ effectiveness at neutralizing HIV.
The study was published in Cell Chemical Biology.