HIV 'fingerprint' tool could greatly assist vaccine development

By Catharine Paddock PhD
    

Scientists hope that their new method of "fingerprinting" the shields of sugar molecules that HIV surrounds itself with to evade the immune system will improve and speed up the development of effective vaccines.

The researchers - from The Scripps Research Institute (TSRI) in La Jolla, CA - report how they developed and tested their HIV fingerprinting tool in the journal Nature Communications.

According to the World Health Organization (WHO), HIV remains a persistent major problem for global public health. To date, the virus has killed more than 35 million people.

Once it enters a person's body, HIV weakens the immune system. The virus impairs and destroys immune cells - especially infection-fighting CD4 cells, or T cells.

As a result, the person becomes increasingly susceptible to a wide range of infections and diseases, including some types of cancer.

There is currently no effective cure for HIV, but it can be controlled with antiretroviral therapy (ART). If properly administered and followed, ART can make a dramatic difference to the lives of infected people and their communities. It can keep them healthy and lower their chances of infecting others.

Challenge for HIV vaccine developers

AIDS is the most advanced stage of HIV infection - it can take 2 to 15 years to reach, depending on the individual. However, if HIV is diagnosed early and the disease is treated before it is too advanced, an infected person can expect to live a healthy, long, and productive life.

Estimates from the Centers for Disease Control and Prevention (CDC) suggest that 1.2 million people in the United States were living with HIV at the end of 2013, including around 1 in 8 who did not know that they were infected.

Great progress has been made in preventing and treating HIV, but there is still much to do, including the search for a vaccine.

Two of the major challenges facing HIV vaccine developers are that the virus is good at hiding from the immune system, and that it keeps changing.

The idea of a vaccine is to stimulate the immune system to produce new or more antibodies against a target on the infecting agent that disables it.

In the case of HIV, vaccine developers suggest that a good target is the glycoprotein envelope that surrounds the virus and contains the machinery that the virus uses to enter host cells.

However, one of the reasons that HIV is so resilient is that it covers its glycoprotein envelope with a shield made of sugar molecules called glycans.

The shield helps the virus to hide from the immune system and stops antibodies from attacking the glycoprotein envelope.

Spotting 'holes' in the glycan shield

Tools that help vaccine developers to deal with the glycan shields are enormously helpful. The new study offers such a tool in the form of a method that analyzes patterns of glycans on the glycoprotein. It allows scientists to quickly "fingerprint" the virus and tell if their vaccine development is on the right track.

An important requirement is the ability to distinguish between high-mannose glycans and complex-type glycans on the glycoprotein envelope. Previous studies have reached this point. However, the new study goes further in that it also identifies glycoprotein sites that have no glycans. In fact, the team found that there are fewer such "holes" in the shield than previously thought.

Finding sites with no glycans is important because vaccine developers can then devise a way to teach the immune system to recognize where the holes in the glycan shield are and produce broadly neutralizing antibodies that attack the underlying envelope.

The new tool is also fast; the team developed algorithms that quickly analyze the results much faster than the manual methods that they were using before. Analysis speed is important in this field as developers are always in a race against time searching for vaccine candidates to fight a virus that evolves rapidly.

Next step: Work with natural forms of HIV

In their study, the researchers used an HIV-like vaccine candidate. They now plan to use the new tool to analyze glycan composition and glycan-free sites on natural forms of HIV.

If the fingerprints match up with what they have, then they will know that they are on the right track.

"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."

-Study leader Prof. James C. Paulson, Department of Molecular Medicine, TSRI

The researchers believe that their approach could also work for other viruses that have a similar glycoprotein envelope, such as the influenza virus.

The new study went some way toward showing this, in that the team also tested the method on an influenza virus protein.

SOURCE: MEDICAL NEWS TODAY