Researchers in South Africa leading a study published recently, suggest their findings offer a new clue toward a possible vaccine against AIDS. They have discovered a vulnerable spot on the outer shell of the human immunodeficiency virus (HIV) that enabled two infected people to make antibodies powerful enough to kill most of the HIV types known around the world.

The ground-breaking discovery, reported online in Nature Medicine on 21 October, offers new clues about how to stimulate the body to produce “broadly neutralizing antibodies”, potent forms of which have only been known about in the last three years. These rare antibodies are thought to be the key to making an AIDS vaccine, because they kill a wide range of HIV types from different parts of the world.

Over the last five years, scientists, many of them working on this study, have been trying to find out how some people infected with HIV manage to develop very powerful immune responses to the virus.

This work led to the discovery of two HIV-infected women from KwaZulu-Natal province in South Africa whose bodies were making broadly neutralizing antibodies.

Long-term follow-ups with the two women that involved numerous lab studies, found that a glycan (a form of sugar) in a specific location on the protein coat that covers the virus (the location is known as position 332) is a weak spot that allows the body to mount an effective attack using broadly neutralizing antibodies.

Lead author Penny Moore, from the University of the Witwatersrand, Johannesburg, and also of the Centre for HIV and STI, National Institute for Communicable Diseases of the National Health Laboratory Service, says in a statement:

“Understanding this elaborate game of ‘cat and mouse’ between HIV and the immune response of the infected person has provided valuable insights into how broadly neutralizing antibodies arise.”

The researchers were surprised to find that in many cases, the virus that caused the initial infection (HIV is constantly mutating under pressure from the body’s immune response) did not have this particular vulnerable spot.

But eventually, under pressure from the host immune responses, the virus changed to one whose outer coat contained the sugar that created the vulnerable spot, which in turn allowed the creation of antibodies that can target it.

Further work with researchers from the University of North Carolina and Harvard University in the US revealed that the weak spot at position 332 may be present in about two-thirds of subtype C viruses, the subtype that is most common in Africa.

The researchers suggest if a vaccine were to target only this particular vulnerable spot, it would be unlikely to be effective against all subtype C viruses, leading to the conclusion that to be effective, an AIDS vaccine will probably have to attack several targets on the virus.

Written by Catharine Paddock PhD