The Scientist : NewsBlog Print: AIDS vaccine trial set to start
The Scientist: NewsBlog:
AIDS vaccine trial set to start
Posted by Bob Grant
[Entry posted at 3rd June 2008 04:34 PM GMT]
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The US government is poised to start a new AIDS vaccine trial, prompting some to caution that it is too soon to initiate such studies after a Merck vaccine not only failed to show effectiveness but also may have increased participants' HIV infection rate.

Late last week, the NIH's AIDS Vaccine Research Subcommittee voted 23-3 in favor of beginning the PAVE 100 HIV vaccine trial. The study would be conducted by the Partnership for AIDS Vaccine Evaluation (PAVE), which is a consortium of government agencies and government-funded organizations involved in HIV vaccine research, and is sponsored by NIAID.

Dennis Burton, a Scripps Research Institute immunologist and member of the advisory panel, urged caution. "We're redesigning the aims of human HIV vaccine research without redesigning the vaccine," Burton, referring to a refocusing of AIDS vaccine research decided upon at an NIH meeting in March, told Bloomberg News. "Let's not go into a human experiment without a clear idea of what we're going to learn."

Yesterday (Jun 2), Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID) director told Bloomberg News that he would review the panel's comments and decide "reasonably soon" whether to proceed with the study. The panel's advice is not the only source from which Fauci will draw in making his decision. Fauci will also consider "the thoughts/recommendations of the various PAVE partners, HIV community groups, other NIAID scientific advisory bodies, such as the Clinical Trials Strategic Working Group," according to an Email sent to The Scientist by an NIAID spokesperson.

The new vaccine - like the failed Merck vaccine - uses a recombinant vaccine based on adenovirus type 5 (Ad5), but administers a single injection after a "prime-boost" of three DNA-based immunizations designed to stimulate the immune system. The failed Merck Ad5 vaccine was administered in three sequential injections, with no prior DNA-based priming. "The [vaccine] regimen is sufficiently different from the Merck product to warrant further testing," Eric Hunter, Emory University vaccinologist and subcommittee chair, said at the panel's meeting.

According to the NIAID, the vaccine will be tested in the US on 2,400 men who have sex with other men, but trial participants must not have detectable Ad5 antibodies and must be circumcised - the two main differences in enrollment criteria from the failed Merck trial.

 

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comment:
No error no correction
by anonymous poster

[Comment posted 2008-06-10 10:32:32]

Dear All

I strongly suggest the trail should commence with HIV positive as the whole world is waiting for breaking news on the cure of HIV/AIDS.

The only way to improve is by trail and error and there are so many HIV positive ready to be used. If it fails, which I doubt, it will review some issues about the virus that will be used for further research and improvement.






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comment:
REVISION: Porceed with PAVE?
by Jesse Creel

[Comment posted 2008-06-06 08:20:08]

Greetings All,

I agree with Dennis Burton of Scripps Research Institute below in (AIDS
vaccine trial set to start ) about the need to consider carefully if PAVE
human trails should proceed.

"We're redesigning the aims of human HIV vaccine research without
redesigning the vaccine,"

"Let's not go into a human experiment without a clear idea of what we're
going to learn."

One PAVE aspect that bears careful consideration is the new version of Ad5
is supposed to get around the preexisting immunity that was a problem in the
Mrk Ad5 STEP trials by screening of trial participants for preexisting
adenoviral immunity. Adenoviral immunity can't be avoided if PAVE is shown
to have the desired trial outcomes and deemed worthy of use in general
unscreened populations. Regardless, there will still be anti-Ad5 vector
immune
responses which could limit vaccine efficacy, as a normal course of the
immune
response events following administration of the Ad5 boost.

Secondly, this ant-Ad5 Vector immune response will squander many important
immune system components, cellular and soluble, that would be better applied
to the chosen vaccine antigens/epitopes. This becomes particularly salient
when you consider the need to vaccinate several billion individuals
worldwide, many of whom have immune systems which are immunosuppressed ...
limited immunologic potentials... as per the case of the HIV+ and/or
malnourished individuals.

The use of multiple boosters becomes extremely logistically
problematic when you consider the need to vaccinate several billion mobile
people around the globe more than once.

The circumcision requirement flies in the face of the real world situation
as
exist in many cultures, circumcision is taboo.

Regarding the 3 DNA primes of the PAVE trial, there is still no convincing
evidence of DNA Vaccine efficacy in humans. I have sent material on this
several times to
the AIDS Vaccine Research Subcommittee and others in the HIV vaccine
development community. I think it unlikely that a DNA vaccine will safely
show efficacy for the foreseeable future, if at all.

Another disappointing HIV Vaccine trial result may make it very difficult to
enroll volunteers for future trials.

Please, let us proceed with extreme caution from here and see if we can't
come up with new and innovative approaches.

Thanking you in advance for considering these out of the traditional vaccine
development box comments.


Jesse Creel

Vaccine Research Advocate
1194 River Valley Dr #3
Flint, MI 48532

Email: JesseCreel@comcast.net




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comment:
some strange math
by Martin Delaney

[Comment posted 2008-06-05 18:19:59]

Bob, I don't understand where you came up with the vote of 23-3 in support of the PAVE trial by the AVRS. I was there. If you add up all the members listed of the committee, including the chair and ex-officios, you get 19 people. Three critics were added for the day to appear more balanced (John Moore, Dennis Burton, Dave Wilkins). Now we've got 22 people. So where does 23-3 come from? And if Moore, Burton and Wilkins were the "only" three voting against the trial, how were they counting Bruce Walker's vote? Anyone who heard him would have a very hard time claiming he was in support of the PAVE 100A. Let's remember that there was a 3rd option in play, that of a much smaller trial of about 750. Several people were in support of the smaller trial rather than the 2500 person juggernaut. The rationale for the larger study over the smaller one kept changing throughout the day.

Much of the enthusiasm for going ahead was based on a new finding that suddenly appeared in the comparative presentation of the VRC and Merck vaccines. Some people thought they heard new evidence that the Merck vaccine had shown an effect on viral load. Others who heard the same presentation, myself included, heard no such thing. The whole presentation of new data went by so fast, and was so dense, that I doubt more than a few people really understood what they were hearing, let alone it's significance. We long ago learned to exercise extreme caution over such preliminary and post hoc analyses. Instead, here people were jumping on it like it was the equivalent of the Dead Sea Scrolls. The acceptance of the new data was way out of proportion to the true value it should be given.

And lets not forget that a great majority of those voting were slated to be participating in the trial. In other words, at least some of their funding was going to come from the study. Was there a single person thus connected to the study who voted against it? Surprise.

As my own testimony that date stated, from my point of view, there is so much wrong with this trial that as it stands now, I'd have a hard time not campaigning against it in the community.




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comment:
Proceed with PAVE?
by Jesse Creel

[Comment posted 2008-06-05 09:44:10]

Greetings All,
I agree with Dennis Burton of Scripps below about the need to consider
carefully if PAVE human trails should proceed.

One PAVE aspect that bears careful consideration is the new version of Ad5
is supposed to get around the preexisting immunity that was a problem in the
Mrk Ad5 STEP trials. This may well be the case for the most part. However
there will still be anti-Ad5 vector immune responses which could limit
vaccine efficacy, as a normal course of immune response events following
administration of the Ad5 boost.

Secondly, this ant-Ad5 Vector immune response will squander many important
immune system components, cellular and soluble, that would be better applied
to the chosen vaccine antigens/epitopes. This becomes particularly salient
when you consider the need to vaccinate several billion individuals
worldwide, many of who have immune systems which are immunosuppressed ...
limited immunologic potentials... as per the case of the HIV+ and/or
malnourished individuals.

Regarding the DNA primes, there is still no convincing evidence of DNA
Vaccine efficacy in humans. I have sent material on this several times to
the AIDS Vaccine Research Subcommittee and others in the HIV vaccine
development community. I think it unlikely that DNA vaccine will safely show
efficacy for the forseeable future if at all.


In conclusion, the use of multiple boosters becomes extremely logistically
problematic when you consider the need to vaccinate several billion mobile
people around the globe more than once.

Thanking you in advance for considering these out of the traditional vaccine
development box comments.


Jesse Creel

Vaccine Research Advocate

1194 River Valley Dr #3

Flint, MI 48532

Email: JesseCreel@comcast.net




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comment:
Error of Making No Trials
by john toeppen

[Comment posted 2008-06-03 13:46:08]

Scientific theories only become theories after a hypothesis is tested by experiment. The words ?trial and error? should be replaced by ?trial and learning experience.? The greatest error is to have no trials and no learning experiences. While this is true for general science, when lives are at risk such a general rule needs to be carefully considered.

One should not make life and death choices for others as a general rule. The notion of informed consent is critical in matters of this kind, not just for this vaccine, but in all human clinical trials. I would expect that there would be some HIV positive people that would like to try anything that offered hope or contributed to an eventual cure. While the notion of doing no harm is an important consideration, many people will die due to the ongoing spreading of this disease. Failure to act is also a very real risk. We should allow volunteers to make informed choices.




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comment:
Unlikely to do harm, may help.
by Ellen Hunt

[Comment posted 2008-06-03 12:47:45]

I am not sanguine about HIV ever having a vaccine, but I support Fauci's decision and think it is the best course for now. I think this trial will show us something very similar to the African trial - at best no detectable effect.

Analyzing these trials is difficult because, let us say that the HIV rate for those in the trial is half of control population. Is that because of the vaccine or behavior? If it is slightly higher, is it because of the vaccine or behavior change for a vaccine that has mild positive effect on a per-contact basis? Can we trust self-reporting by subjects? I'm not sure we can overall.

My expectation is that this vaccine, like the previous, will have no meaningful effect. That will teach us something. But no meaningful effect is not harm. HIV is hard to acquire, even MSM high risk subjects have an average of 200 contacts to get infected. So even if the vaccine raises susceptibility to HIV slightly, to class that as harm in the Hippocratic sense is a stretch.

But perhaps this vaccine may work. I think that is quite unlikely, but if it does the benefit is very large. Weighing no harm against potentially great benefit, I completely support Fauci's decision.




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