Novel Method Fingerprints HIV

Technique will help scientists develop an effective HIV vaccine.

Fully eradicating HIV from the body is an ongoing challenge because of the virus’ ability to evade the immune system and block attacks from antibodies.

In a study published in Nature Communications, investigators developed a method to analyze the protective shield that surrounds the virus.

Glycans are sugar molecules that form a shield on HIV’s protective outer glycoprotein machinery, which HIV uses to enter host cells. To stop the infection, the immune system wants to produce antibodies that bind to the glycoprotein. Unfortunately, the glycans block the immune cells from recognizing their targets and developing useful antibodies.

Using the novel method, scientists can rapidly create a “fingerprint" of the glycans on the glycoprotein to determine if they are on the right track in 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,” said lead investigators James Paulson, Cecil H., and Ida M. Green.

The new method allows scientists to identify which types of glycans make up the glycoprotein, and whether the glycoprotein has any vulnerable holes.

At the Scripps Research Institute, several investigative teams are designing HIV vaccines that prompt the body to create rare broadly neutralizing antibodies that can get around the glycan. To do this, they need to introduce the immune system to HIV-like glycoproteins and teach it to locate where the holes in the shield are.

In the current study, investigators developed a way to determine the composition of sugars on the glycoprotein. They used enzymes to break the glycoprotein into smaller peptide chunks. The peptide chunks were analyzed using mass spectrometry to see if they fall into 1 of 3 categories: high-mannose glycans, complex-type glycans, or sites with no glycans.

Although prior studies have been able to differentiate between high-mannose and complex-type glycans, this was the first-time investigators could also see the number of glycan-free sites.

Interestingly, the investigators found that the glycoprotein does not have as many holes as they predicted

In addition to identifying glycan-free sites, the new method also cuts down on time. Prior studies using mass spectrometry required investigators to manually analyze the peptide results, a process that could take months. In the new study, investigators used a computer algorithm to rapidly analyze the results.

The increase in speed will aid scientists as they begin to sort through different HIV vaccine candidates to identify the right one, the authors noted.

Next, the investigators plan to analyze the glycan composition and glycan-free sites on the native form of HIV, not just as an HIV-like candidate. Paulson added, “then we can see if the fingerprints match up.”

The match will indicate to investigators that they are on the right path in developing an HIV vaccine. The authors noted that the novel method could also be used against viruses with a similar glycoprotein shield, such as influenza.