HIV ‘fingerprint’ tool could greatly assist vaccine development

By Catharine Paddock

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

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

Spotting ‘holes’ in the glycan

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
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.

Kayode Ojo
Kayode Emmanuel Ojo is the Co-Founder and Managing Director at SHEFFA Limited. He is presently studying Computer Science at the National Open University, Victoria Island, Lagos.