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Two Wits researchers led an AIDS
study published today in the journal, Nature Medicine, which describes how a
unique change in the outer covering of the virus found in two HIV infected
South African women enabled them to make potent antibodies which are able to
kill up to 88% of HIV types from around the world.
This ground-breaking discovery
provides an important new approach that could be useful in making an AIDS
vaccine.
The study, performed by members of
the Centre for the Aids Programme of Research in South Africa (CAPRISA)
consortium, involves scientists from Wits University, the National Institute
for Communicable Diseases (NICD) in Johannesburg, the University of
KwaZulu-Natal and the University of Cape Town, who has been studying, over the
last five years, how certain HIV-infected people develop very powerful antibody
responses.
These antibodies are referred to as
broadly neutralising antibodies because they kill a wide range of HIV types
from different parts of the world. This CAPRISA team initially discovered that
two KwaZulu-Natal women, one of whom participated in the CAPRISA 004 tenofovir
gel study, could make these rare antibodies.
Through long-term follow-up
laboratory studies on these two women, the team led by Wits researchers and
Centre for HIV and STI at the National Institute for Communicable Diseases of
the National Health Laboratory Service based scientists Dr Penny Moore and
Professor Lynn Morris, discovered that a sugar (known as a glycan) on the
surface protein coat of the virus at a specific position (referred to as
position 332) forms a site of vulnerability in the virus and enables the body
to mount a broadly neutralizing antibody response.
“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,”
says Moore.
Morris, Head of AIDS Research at the NICD
explained: “We were surprised to find that the virus that caused infection in
many cases did not have this antibody target on its outer covering. But over
time, the virus was pressured by 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”.
“Broadly neutralising antibodies are
considered to be the key to making an AIDS vaccine. This discovery provides new
clues on how vaccines could be designed to elicit broadly neutralising
antibodies. The world needs an effective AIDS vaccine to overcome the global
scourge of AIDS,” said Professor Salim Abdool Karim, Director of CAPRISA and
President of the Medical Research Council, in his comments on the significance
of the finding.
While their existence has been known
for a while, highly potent forms of broadly neutralizing antibodies against HIV
were only identified about 3 years ago. Until now, it was not known how the
human body is able to make broadly neutralizing antibodies.
This study discovered one mechanism
by which these antibodies may be made. To make this discovery, the research
team studied the target of some of these antibodies, a sugar that coats the
surface protein of HIV, forming a site of vulnerability. By tracing back the
evolution of the virus that elicited these antibodies, this team showed that
this particular weak point was absent from the virus that first infected these
women.
However, under constant pressure
from other less powerful antibodies that develop in all infected people, their
HIV was forced to expose this vulnerability over time. This allowed the broadly
neutralizing antibodies to develop.
Analysis of a large number of other viruses from
throughout the world, performed in collaboration with scientists from the
University of North Carolina and Harvard University, suggest that the
vulnerability at position 332 may be present at the time of infection in about
two thirds of subtype C viruses (the subtype most common in Africa). Hence, if
a vaccine is developed to target this glycan only, it may not be able to
uniformly neutralize all subtype C viruses; as a result AIDS vaccines may need
to attack multiple targets on the virus.
The Friends of AIDS Foundation is
dedicated to enhancing the quality of life for HIV positive individuals and
empowering people to make healthy choices to prevent the spread of the HIV
virus. To learn more about The Friends of AIDS Foundation, please visit: http://www.friendsofaids.org.
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