The science of coincidences

2012-10-27 15:32

How two women and the powerful antibodies in their blood may hold the key to discovering an HIV vaccine

It could become one of the most powerful weapons in the fight against HIV/Aids, and it started as a series of coincidences.

Seven years ago, two women enrolled in different HIV trials conducted by the Centre for the Aids Programme of Research in SA in KwaZulu-Natal.

One was a 43-year-old mother of two living in Durban and the other was a 22-year-old living in the remote village, Vulindlela, near Pietermaritzburg.

Today, their stories – and the powerful antibodies hidden in their blood – might, scientists believe, be the first step on the road towards developing an HIV vaccine.

If they are right, the vaccine would combat HIV-1, the strain of the virus that is the most common.

The two women are among a rare group of HIV-infected people across the world who are able to produce powerful antibodies that kill HIV.

These are known as broadly cross-neutralising antibodies and can be produced years after someone is infected.

The antibodies can kill up to 88% of HIV strains from across the world, and unlocking their secrets could help scientists successfully produce a vaccine.

Researchers did not know how some immune systems produced these antibodies and what role the HI virus itself plays in their development.

After the two infected women crossed paths with a team of mostly young scientists from South Africa’s National Institute for Communicable Diseases, the researchers from the institute quite accidentally solved the mystery.

The breakthrough came about 18 months ago while they conducted laboratory studies to understand which part of the HI virus is targeted by broadly cross-neutralising antibodies.

The team, led by Dr Penny Moore and Professor Lynn Morris, discovered that the women’s antibodies targeted a specific sugar on the HI virus known as “332”.

They then went back and studied the first blood samples taken shortly after the women were infected.

To their surprise, they discovered that the virus that had infected the women carried no 332 sugar, even though later antibodies were binding to that particular sugar.

Moore said: “As a virologist, this fascinated me.

“We shifted our focus to this new discovery. We found that the immune system forced the virus to put the 332 sugar on the outer coating of the virus and this sugar made the virus vulnerable and enabled the broadly cross-neutralising antibodies to attack and kill it.”

Morris, who heads Aids research at the institute, said they were also surprised to find that the virus that caused infection in many cases did not have this antibody target on its outer covering.

Over time, though, “the virus was pressured by the body’s immune reaction to cover itself with the sugar that formed a point of vulnerability, and so allowed the development of antibodies that hit that weak spot”, Morris explained.

Understanding how this vulnerability happens is what makes scientists believe the development of a vaccine

could finally be within reach.

The HI virus is extremely adaptable.

For more than 30 years, scientists have tried to develop a vaccine to fight it.

But its ability to hide from normal antibodies means all vaccines have so far failed.

The HI virus coats itself with sugars to avoid strain-specific antibodies and also keeps evolving.

This is why broadly cross-neutralising antibodies, and what the institute team has learnt about them, are so

critical to winning the fight.

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