ISIS Report 11/10/07
New Strategy HIV Vaccine Fails
More Infected with HIV
This latest failure heightens concerns that the vaccine strategy may be
fundamentally flawed and hence unsafe and unethical. Full disclosure of clinical
and scientific data must be made mandatory. Dr.
Mae-Wan Ho
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AIDS vaccines that do more harm than good
Vaccines supposed to protect
against HIV infections and AIDS disease could do more harm than good, as ISIS
has warned on many occasions (see for example,
AIDS Vaccines Worse Than Useless?
SiS 19; Unraveling AIDS, ISIS
Report) [1,2].
Another HIV vaccine has
failed.
On 21
September 2007, the pharmaceutical giant Merck called a halt to a phase II
trial of a new vaccine candidate against HIV [3]. An interim assessment showed
that the vaccine, long considered the most promising in development, failed
both in preventing HIV infection and in reducing the viral load of those infected.
The vaccine candidate
(Merck V520) is a mixture of three components, each a weakened adenovirus
vector carrying one of the three synthetic HIV genes gag, pol
and nef. The vaccine is designed
to elicit a cell-mediated immune response, to stimulate the body’s own CD8
T-cells that recognize and kill the HIV-infected cells. No further details
on the precise nature of the vaccine could be found on the Merck website or
in the published scientific literature.
The multi-centre,
randomised, double-blind, placebo-controlled phase II trial enrolled 3 000
HIV-negative volunteers from diverse background between 18 and 45 years of
age at high risk of HIV infection.
The interim assessment
was on approximately 1 500 volunteers expected to have the best response to
the vaccine because they had low levels of pre-existing immunity to adenovirus
5.
The results were devastating.
The vaccine did not prevent infection, if anything there were more infections
among those given the vaccine. In 741 volunteers who received at least
one dose of the three-dose vaccine series, 24 cases of HIV infection were
found, compared to 21 cases of HIV infection in the 762 of the placebo group.
In the subgroup of 672 who had received at least two vaccinations and who
were HIV negative for at least the first 12 weeks of the trial, 19 cases of
HIV infection were found, compared to 11 cases in the 691 volunteers who received
placebo. The vaccine did not reduce the amount of virus in the bloodstream
of those who became infected. The HIV RNA levels at approximately 8 to 12
weeks after diagnosis of infection expressed as geometric means were about
40 000 copies/mL in the vaccine group and 37 000 copies/mL in the placebo
group.
Concern over the ethics of vaccine trials heightens as doubt gathers over
the vaccine strategy
This latest vaccine failure
came less than two months after headlines resounded across the globe that
the world is losing the fight against AIDS. Anthony Fauci, director of the
National Institute of Allergy and Infectious Diseases and US’ top advisor
on AIDS, said at the 4th International AIDS Society Conference
held in Sydney Australia that for everyone one person placed on therapy, six
people get infected with HIV; and he agreed with the UNAIDS Executive Director
Peter Piot that the discrepancy between the number of individuals being put
on therapy and the number becoming infected “is not sustainable”, and means
that “we are losing the battle” against HIV and AIDS [4]. Fauci later qualified
his remarks by referring to “advances” made, including new approaches in vaccine
development.
The failure of the Merck vaccine heightens ethical concerns over the continuation
of a range of HIV vaccine trials, and raises doubt over the vaccine strategy
itself [2], as both old and new approaches to vaccine development are increasingly
mired in controversy [5] (see Controversy
over European Framework Programme AIDS Vaccines, SiS 36).
The International AIDS Vaccine
Initiative (IAVI) recognizes “challenges” facing an AIDS vaccine [6], chief
among which is the hypervariability of HIV both on a population basis and
within HIV-infected individuals, the virus can differ between tissue compartments
within the same individual host, and several forms could co-exist in the same
tissue compartment. The other challenges are that both the immune response
to the virus and how it causes disease remain poorly understood; and there
are multiple routes of transmission, which complicates the vaccine strategy.
One main feature against
the vaccine strategy is that HIV is a retrovirus that integrates into the
host cell genome, and could remain in a latent form, thereby escaping immune
surveillance [7, 8]. The virus’ homologies to host genes could also provoke
autoimmune responses against the host.
An international team of
scientists led by Vejkov Veljokovic at the Institute for Nuclear Sciences
Belgrade in Serbia reviewed the evidence on the hazards of gp120 vaccines extensively in 2000 [9]. They
highlighted the homologies of gp120
to the human immunoglubulins, hence its potential for participating in, and
destabilizing, the immune network. Gp120-based
vaccines caused ‘deceptive imprinting’ of the immune system, disarming it
against a subsequent HIV infection and accelerating progression to AIDS disease.
Such vaccines were also found to elicit auto-antibodies in the host, to impair
cytotoxic T lymphocytes, and to eliminate CD4+ T cells. Further, the presence
of recombination hotspots in gp120
facilitates horizontal gene transfer and recombination to create new HIV strains
and other viruses and bacteria. (The dangers of horizontal gene transfer and
recombination apply to all recombinant vaccines against HIV.) On the basis
of the extensive evidence of actual and potential hazards, Veljkovic and colleagues
called for a moratorium on gp120
vaccines, and for a new vaccine strategy that avoids the dangers specific
to gp120, as well as those general to HIV as
an integrated retrovirus.
Above all, it remains unclear
as to exactly how HIV causes AIDS disease, as IAVI admits (see above) and
as borne out by a recent review of the evidence [10, 11] (On Quitting HIV, Beyond the HIV-Causes-AIDS
Model, SiS 34). In the absence
of this knowledge, any vaccine strategy based on HIV is inappropriate and
potentially dangerous.
A rethink of the vaccine
strategy is in order in view of the harm that can be caused to participants
in clinical trials; and the failed Merck vaccine is perhaps the clearest example
of that to-date. Bearing in mind that only a subset of the volunteers – those
expected to give the best response to the vaccine – has been assessed, the
full clinical picture could be considerably worse.
Merck should now disclose the results in full, including the
precise nature of the vaccine used, to ensure that the same mistakes are not
made again. For the same reasons, full reporting of the clinical and scientific
data from all vaccine trials should be made mandatory.
Disproportionate resources poured into anti-HIV vaccines at the expense of
other safer and more effective interventions
There is now substantial evidence that nutritional interventions
and exercise are effective in both preventing HIV infection and in delaying
disease progression, as described in many chapters of our report, Unraveling AIDS [2]. Since
then, new supporting evidence has accumulated.
Naturally occurring flavonoids
in tea and fruit juices are found to have anti-HIV activity [12, 13] (Desk Top Drug Discovery,
SiS 33); while certain naturally
circulating auto-antibodies in HIV-negative healthy individuals are capable
of neutralising HIV [14]. The enormous amounts of resources that continue
to be poured into vaccine development via the IAVI, especially by mega-philanthropies
such as the Gates Foundation [15] (Philanthropy Gates Style,
SiS 35) would do much more to
combat AIDS if diverted to eradicating poverty, improving nutrition and sanitation,
and to promoting a generally healthy lifestyle.
I thank
Dr. Veljko Veljkovic for his advice and for sending me key publications for
this report.
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