Clinical trials hint that treatment strategy is not a dead end.
vaccines help HIV patients in countries without ready access to
The world buzzed last week with news that an antiretroviral gel
can halve the incidence of HIV infection in women (see Nature doi:10.1038/news.2010.363; 2010).
But a quieter buzz could be heard at the International AIDS
Conference (AIDS 2010) in
Vienna, where the gel results were unveiled. At a special session,
included in the programme at the last minute, attendees heard the
results of a handful of successful, but small, early-phase clinical
trials for therapeutic vaccines — once thought to be a dead end for
Normal vaccines are designed to prevent infections, but so far
none has worked for HIV. Therapeutic vaccines, in contrast, aim to
treat infected people — in the case of HIV, by boosting ravaged
immune systems. Initial clinical trials in the 1990s were
disappointing, however, and the vaccines fell from scientific
Drug combinations that decrease viral concentrations have become
the main method of treating HIV, but they do not completely
suppress the underlying disease. "They leave patients with a level
of harmful immune activation, which can cause premature ageing,"
says Joep Lange, a clinical virologist from the University of
Amsterdam and a former president of the International AIDS Society.
"The therapeutic vaccine approach may help with this", he says, by
modifying immune responses.
Lange is encouraged by the trial results, but cautions that the
trials so far are small, and that even if the vaccines work they
will never replace drugs. Some key AIDS researchers continue to
believe that therapeutic vaccines will not prove helpful in the
All of the vaccines, which were developed by several small
biotechnology companies, modestly but significantly reduced viral
levels in the blood of patients, who responded for months or
longer. In some cases, the vaccines also increased levels of
CD4+ T cells — the vital immune-regulator cells that HIV
depletes. In theory, the vaccines would only need to be
administered every few months.
Two of the phase II trials reported at the meeting focused on
improving the efficiency of the immune system's dendritic cells.
These are the cells that present foreign antigens — in this case,
HIV proteins — to T cells so that they can recognize and eliminate
One approach, developed by Genetic Immunity, a
biotechnology company based in Budapest, involves creating
nanoparticles that contain selected pieces of RNA from HIV. The
preparation is applied to patients by means of a skin patch. The
skin below the patch is first slightly damaged to attract
precursors of dendritic cells, exposing them to 15 HIV proteins
transcribed from the RNA.
The other tactic, from Argos Therapeutics of
Durham, North Carolina, relies on tailor-made vaccines for each
patient. The researchers extracted dendritic cells and viral RNA
from patients, then loaded the cells with the RNA before putting
them back into the same patient.
Therapeutic vaccines are normally tested in patients who are
already undergoing drug treatment. To avoid the drugs confounding
the results, patients are required to take a drug 'holiday' for the
few months of the trial. But a placebo-controlled clinical trial by
FIT Biotech of Tampere,
Finland, broke with that model by recruiting 60 patients in South
Africa who had never been treated with drugs.
The FIT vaccine comprises a combination of gene fragments
designed to make the patient immune to six viral proteins. In
around 80% of patients receiving treatment, the virus was
suppressed and CD4+ levels were maintained two years
after therapy began.
The results are particularly relevant to countries such as South
Africa, where many patients do not have easy access to drugs, says
Eftyhia Vardas, a virologist at the University of the
Witwatersrand, who ran the clinical trial in 2006 in Soweto,
Johannesburg. Vardas recalls feeling like a 'maverick' when she
agreed to take on the trial. At the time, the South African
government officially denied that HIV caused AIDS, and her
scientific colleagues didn't believe that therapeutic vaccines held
any promise. She was sceptical herself, she says, having seen other
"But you can't shut doors when options are so limited," she
says. South Africa is home to 5.7 million HIV-infected people.
A vaccine, says Vardas, "would help South Africa to be able to
delay onset of AIDS and reduce infectivity by keeping viral loads
low when drugs are not so widely available".
The ultimate value of the vaccines will only become clear as
larger phase III trials roll out over the next few years. For now,
leaders in AIDS research are cautious about the results. Anthony
Fauci, director of the US National Institute of Allergy and
Infectious Diseases (NIAID) in Bethesda, Maryland, says that he
could imagine a role for "a good therapeutic vaccine" in patients
who have been treated early in their disease, and therefore have
only a small reservoir of HIV, and whose blood levels of HIV are
completely suppressed by drugs. But he warns that because the
vaccines caused only a modest decrease in viral load, using them in
place of drugs could allow viruses to mutate beyond the control of
the vaccine. "These early trials involve small numbers of people,"
adds Carl Dieffenbach, head of the NIAID AIDS division. "It would
be wrong to foster false hopes."
But the Maryland-based advocacy group National Association of
People with AIDS, whose vice-president of community affairs,
Stephen Bailous, organized the special session, has championed the
approach. "We need to have hopes and some of the therapeutic
vaccines look really promising," says Bailous. "If we can't raise
our hopes there, then where?"
Published online 27 July 2010 | Nature 466,
539 (2010) | doi:10.1038/466539a