At an ill-fated press conference in 1984, US Health and Human Services
Secretary Margaret Heckler boldly predicted an effective AIDS vaccine would be
available within just two years.
But a string of failed attempts -
punctuated by a 2007 trial in which a Merck vaccine appeared to make people
more vulnerable to infection, not less - cast a shadow over AIDS vaccine
research that has taken years to dispel.
A 2009 clinical trial in Thailand
was the first to show it was possible to prevent HIV infection in humans. Since
then, discoveries have pointed to even more powerful vaccines using
HIV-fighting antibodies. Now scientists believe a licensed vaccine is within
reach.
"We know the face of the
enemy," said Dr. Barton Haynes, of Duke University in Durham, North
Carolina, and recent director of the Center for HIV AIDS Vaccine Immunology
(CHAVI). The research consortium was funded by the National Institute of
Allergy and Infectious Diseases (NIAID), founded in 2005 by the National
Institutes of Health to identify and overcome roadblocks in the design of
vaccines for the human immunodeficiency virus, which causes AIDS. NIAID's
funding of CHAVI ended in June.
Unlike many viruses behind
infectious disease, HIV is a moving target, constantly spitting out slightly
different versions of itself, with different strains affecting different
populations around the world. The virus is especially pernicious since it
attacks the immune system, the very mechanism the body needs to fight back.
"The virus is far more
crafty than we ever thought," said Haynes, who will outline progress in
vaccine research at the International AIDS Society's 2012 conference being held
in Washington from July 22-27.
First sign of hope
Thanks to drugs that can control
the virus for decades, AIDS is no longer a death sentence. New infections have
fallen by 21 per cent since the peak of the pandemic in 1997 and advances in
prevention - through voluntary circumcision programs, prevention of
mother-to-child transmission and early treatment - promise to cut that rate
even more.
Still, as many as 34 million
people are infected with HIV worldwide. And with 2.7 million new infections in
2010 alone, experts say a vaccine is still the best hope for eradicating AIDS.
Teams have been working on a
vaccine for nearly three decades, but it wasn't until RV144, the 2009 clinical
trial involving more than 16,000 adults in Thailand, that researchers achieved
any hint of success.
The test of a combination of two
vaccines followed several big failures, including the stunning news that
Merck's vaccine may have increased the risk of infection among men who were
both uncircumcised and had prior exposure to the virus used in the vaccine.
"It had an extremely
chilling effect on the whole field," said Colonel Nelson Michael, director
of the US Military HIV Research Program at the Walter Reed Army Institute of
Research, which led the RV144 trial.
The Thai study tested Sanofi's
ALVAC, a weakened canary pox virus used to sneak three HIV genes into the body,
and AIDSVAX, a vaccine originally made by Roche Holding's Genentech that
carried an HIV surface protein.
Both vaccines had poor showings
in individual trials. Researchers were so convinced the Thai trial would fail
that 22 scientists wrote an editorial in Science calling it a waste of money.
Then came the shocker. Results of
the study published in 2009 showed the vaccine combination cut HIV infections
by 31.2 per cent. According to Michael and many other experts, the result was
not big enough to be considered effective, but its impact on researchers was
huge, says Wayne Koff, chief scientific officer of the International AIDS
Vaccine Initiative (IAVI) based in New York.
An extensive analysis of the Thai
trial published this year in the New England Journal of Medicine offered clues
about why some volunteers responded.
The study, led by Haynes,
scientists at Walter Reed and 25 other institutions, found men and women who
were vaccinated made antibodies to a specific region of the virus's outer coat,
suggesting this region provides an important vaccine target.
Preparations are under way for a
follow-up trial testing beefed-up versions of the vaccines among heterosexuals
in South Africa and men who have sex with men in Thailand.
Once again, the trial will use a
Sanofi vaccine, but instead of AIDSVAX, researchers will use a different
vaccine candidate with a boosting agent from Novartis.
Michael said it has been a major
effort to secure new research partners and funding, including support from host
countries, as well as to persuade rivals Novartis and Sanofi to work together.
The teams still need to retool the vaccines to work in South Africa, where the
strain of HIV is different.
"We're really working as
fast as we can," said Michael, who expects large-scale effectiveness
studies to start in 2016.
The hope is to have at least 50
per cent effectiveness, a level that mathematical modelers say could have a
major impact on the epidemic. Michael thinks this might be the pathway for
getting the first HIV vaccine licensed, possibly by 2019.
Vaccine experts are equally
excited about a vaccine that Michael's team is developing with Harvard
University and Johnson & Johnson's Crucell unit, which uses weakened
versions of a common cold virus and a smallpox virus.
A study published in February
showed this vaccine protected monkeys from a virulent strain of HIV. Animals
that did become infected after repeated exposure also had low levels of virus
in their blood. Safety studies in human patients are just starting, with
large-scale efficacy studies slated for 2016.
Next generation vaccines
The current crop of vaccines is
largely designed to train immune system cells known as T-cells to recognize and
kill cells already infected with HIV. While these trials progress, scientists
are working on even more advanced vaccines that activate powerful antibodies to
prevent HIV from infecting cells in the first place. Both would be administered
before a person becomes exposed to the virus.
Most modern vaccines use this
antibody approach, but HIV's extreme skill at mutating makes it difficult for
specifically targeted antibodies to identify and neutralize the virus.
Teams led by Dr. Dennis Burton of
the Scripps Research Institute in La Jolla, California, Dr. Michel Nussenzweig
at Rockefeller University in New York, Dr. Gary Nabel of NIAID's Vaccine
Research Center, Haynes at Duke and others have focused on rare antibodies made
by 10 to 20 per cent of people with HIV that can neutralize a broad array of
strains.
Researchers think a vaccine that
can coax the body into making these antibodies before HIV exposure would offer
a powerful foil to many forms of the virus.
Such antibodies seek out and
latch on to regions of the virus that are highly "conserved," meaning
they are so critical to the virus that they appear in nearly every HIV strain.
By attaching to the virus they make it incapable of infecting other cells.
Until 2009, scientists had
identified only a few broadly neutralizing antibodies, but in the past few
years teams have found dozens.
So far, scientists have isolated
the antibodies, identified what part of HIV they target and even know the exact
shape they make, Koff said. Researchers are now using this information to
design vaccines that prompt the immune system to make them.
"We're not there yet,"
Nabel said.
NIAID this month said it will
spend up to US$186 million (S$235 million) over the next seven years to fund
the Centers for HIV/AIDS Vaccine Immunology & Immunogen Discovery. The new
consortium is focused on making vaccines that induce these protective
antibodies, with major grants going to Duke and Scripps.
Nabel said no vaccine being
tested today "is likely to hit it out of the park," but many
researchers do feel advances in broadly neutralizing antibodies are key to
developing a highly successful HIV vaccine.
"It's really a new day when
we start to think about where we are with AIDS vaccines," Nabel said.
Reuters
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