Novel Approach May Revolutionize Creation of HIV Vaccine

Determining the composition of HIV’s glycoprotein can help fight the virus.

HIV is able to harness the body’s cells to disguise itself from the immune system to prevent antibodies from attacking it, which has made preventing the virus difficult. Specifically, HIV can use a shield of glycans—sugar molecules— to take hold in the body.

The authors of a new study have developed a way to “fingerprint” HIV that is disguised by a glycan shield. The novel approach involves analyzing the glycan shield on HIV’s outer glycoprotein, which is being developed as a vaccine candidate.

With this approach, the authors were able to develop a fingerprint of the glycans on the glycoprotein to determine if a vaccine candidate is effective, according to a study published by Nature Communications. This method could significantly increase the likelihood of developing an effective HIV 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 researcher James Paulson, PhD.

This innovative approach allowed the authors to see which glycans compose the glycoprotein, and if there are any spots vulnerable to attack.

The glycans cover the glycoprotein machinery that is used by HIV to infect healthy cells. While the immune system wants to create antibodies that bind to the glycoprotein to inhibit infection, the glycans block immune cells from seeing their target and creating the proper antibodies, according to the study.

Numerous research teams have been developing HIV vaccine candidates that cause the body to create broadly neutralizing antibodies that can bypass the glycan shield. To do this, the immune system must be exposed to HIV-like glycoproteins and taught where there are holes in the shield.

In the study, the authors created a novel way to determine the composition of the glycan shield to increase the efficacy of candidate vaccines.

First, the investigators used enzymes to break down the glycoprotein into smaller parts. Then, they used mass spectrometry to analyze the small peptide chunks to determine if they were: high-mannose glycans (a type with a specific sugar), complex-type glycans (more mature glycans), or a site without glycans, according to the study.

This was the first time glycan-free sites have been discovered. The approach also revealed that the glycoprotein does not have as many holes as expected.

Additionally, the novel method also was reported to save time. Previous studies required a manual analysis of peptide results from mass spectrometry. However, in the new study, the authors were able to develop a computer algorithm to conduct a rapid analysis.

The authors predict that the more rapid analysis will help scientists sift through HIV vaccine candidates to discover the ones that will prevent a majority of strains, according to the study.

Next steps include analyzing the glycan composition and glycan-free sites in natural HIV rather than HIV-like vaccine candidates.

“Then we can see if the fingerprints match up,” Dr Paulson said.

The authors said that if the fingerprints match, they are confident that they are developing an effective vaccine that can elicit broadly neutralizing antibodies.

This approach could also be useful to combat other viruses that utilize a glycan shield, such as influenza, since the authors have already successfully tested it on an influenza protein, the study concluded.