Researchers have developed a new method to “fingerprint” HIV by attacking the its defense mechanism.
HIV is often “hidden” by a shield of sugar molecules called glycans that can conceal the virus from the immune system and block antibodies from attacking it.
However, scientists at The Scripps Research Institute (TSRI) have developed a method to analyze the glycan shield on the protective outer glycoprotein of HIV, a finding that could lead to a better HIV vaccine candidate.
The method allows scientists to rapidly create a ‘fingerprint’ of the glycans on the glycoprotein and identify if they are on the right track to developing an effective vaccine.
“The ability to identify the glycan fingerprint on HIV’s glycoprotein will help us develop a vaccine that matches what is found on the virus,” James Paulson, the Cecil H. and Ida M. Green Chair of Chemistry at TSRI and co-chair of the Department of Molecular Medicine, who led the study, said in a statement.
The new method allows scientists to finally see which types of glycans make up the glycoprotein and whether the glycoprotein has any vulnerable holes. The human immune system wants to produce antibodies that bind to the glycoprotein to stop infection, but the glycans block immune cells from seeing their targets and developing useful antibodies.
Researchers previously designed HIV vaccines that prompt the body to create rare “broadly neutralizing” antibodies that can actually get around the glycan shield by introducing the immune system to HIV-like glycoproteins and teaching the immune system where the holes in the shield are.
In the new study, they developed a way to figure out the composition of sugars on the glycoprotein. They used enzymes to break the glycoprotein into smaller peptide chunks and then used a technique called mass spectrometry to analyze these peptides.
They were put into three categories—high-mannose glycans (a type with a specific kind of sugar), a complex-type glycans (more mature glycans) or sites with no glycans. Previous studies had distinguished between high-mannose and complex-type glycan, but this is the first time scientists could also see the number of glycan-free sites.
The new method also revealed that the glycoprotein does not have as many holes as many researchers had predicted.
Previous studies using mass spectrometry had required researchers to manually analyze the peptide results—a process that could take months.
However, the researchers successfully used a compute algorithm to rapidly analyze the results.
The speed will allow the scientists to sort through many HIV vaccine candidates to find the right ones to prevent a wide-range of ever-evolving HIV strains.
The researchers will now analyze the glycan composition and glycan-free sites on the natural or “native” form of HIV.
“Then we can see if the fingerprints match up,” Paulson said, adding that if they do match up, the researchers will know they are on a path to developing a vaccine that can induce useful antibodies.
The new method could also be used to fight against viruses with a similar glycoprotein shield including influenza.