Thursday, October 11, 2007

Giving journalists a bad name.

The linked article sums up typical AIDS denialist thinking. You leap all over a perceived failure of mainstream science (ignoring the fact that 80% of new drug discoveries fail), drag out disproven denialist claims, quote two well-known AIDS denialists and sit back looking smarmy.

Except that the author completely failed to understand the vaccine in question and how it worked, and why it was supposed to work, and therefore based the entire article (which was a diatribe on HIV antibodies) on a false premise. I am astounded. It took me less than 30 seconds of research (I googled the vaccine name) to find that the author has misunderstood the study. Or rather, Ms Maggiore had misunderstood the study perhaps and he had believed her. Whether he did so out of laziness or out of a personal belief in Ms Maggiore's cause I cannot say, but either way it's terrible journalism.

I wrote in, and just in case my comment gets rejected, here it is anyway to explain to the average reader why the author, Maggiore and Duesberg are completely off-track.

Err, since when have antibodies been a marker of immune success, and since when have antibodies been "the problem" of AIDS?

Neither Duesberg nor Maggiore knows what they're talking about.

And neither does the author of this article. The vaccine MrkAd5 HIV-1 is not supposed to produce anti-HIV antibodies, but instead produces anti-HIV T cell responses. The same kind of T cell responses that are shown to protect people against HIV infection and slow down progression to AIDS - as predicted by mainstream AIDS scientists but going against the theories of Duesberg, Maggoire and the like.

Please get your facts straight and stop pandering to pseudoscience for the sake of an "exciting" story. You give journalists a bad name.


Blogger Unknown said...

Hello Dr. Bennett,

Above you write, “... the author... based the entire article (which was a diatribe on HIV antibodies) on a false premise.”

What exactly is the false premise you talk about? Is this false premise stated in the author’s article?



4:39 PM  
Blogger Bennett said...

The premise is that the vaccine was designed to produce anti-HIV antibodies. It wasn't. The premise is obvious from the article's content...

"The idea is that because of these cold viruses the body will create antibodies that will effectively protect against the presence of HIV."

Err. No.

As the link I provided says:

"Studies in animals have demonstrated that immunization with recombinant adenovirus vectors is an efficient way to elicit HIV-specific cell mediated immune (CMI) responses."

The author should have said "The idea is that because of these cold viruses the body will create KILLER T CELLS that will effectively protect against the presence of HIV." (correction in caps)

But if the author had done that, it would have made no sense to go on and write a diatribe about antibodies... The whole content of the article reeks of rehashed disproven denialist arguments and quotes presented as something novel. Sad really.

6:55 PM  
Blogger Moore said...

Dr. Bennett,

I think you are right, the author and possibly Duesberg and Maggiore as well, took a general swipe at HIV vaccine approaches without being specific about the trial in

However, I'm chagrined to discover that the denialists' lack of rigour has infected you as well, Dr. Bennett. Merely because a vaccine is supposed to evoke a cell-mediated immune reponse, it doesn't mean an antibody reponse is excluded.

About the vaccine in question HVTN has this to say:

"Entry 7:
The study vaccine is designed to work by mimicking the shapes and structures of HIV. The study vaccine allows the body to make HIV proteins that may cause a response from the immune system. During this response, the immune system may produce antibodies and cellular (lymphocyte) responses that recognize HIV without ever actually being exposed to HIV.

Entry 17:
The study vaccine will likely cause a false positive result on a standard HIV test (see Question 18), and such a result may lead to being treated unfairly by others. The study site can provide free testing for as long as participants need it to tell the difference between HIV infection and a positive result caused by the study vaccine."

It would seem, Dr. Bennett, that, in this case at least, the principle behind CMI is that the (snippets of?) genes introduced via the adeno vectors are supposed to code for proteins that are then presented to the lymphocytes. These proteins, as you can see, are logically enough the very same that evoke antibody responses.
So this vaccine was expected to evoke antibodies, just as the denialists claim, although they do not seem to be very well informed about the STEP trials

But I have a futher question that may be nearer your area of expertise. In entry 18 of the above referenced document it says:

"There are other types of HIV tests that look for the presence of the virus instead of the presence of antibodies. Participants are counseled to get HIV testing done only at their trial site because the site has access to specific tests that can differentiate between vaccine-induced positives and true HIV infection."

Could you tell us which test distinguishes between a vaccine- induced (false)positive and true

11:34 AM  
Blogger Bennett said...

I never said an antibody response was excluded, I merely stated that it wasn't the point of this particular vaccine ;-)

I also think that some of the "quotes" from Maggiore and Duesberg "in response" to the vaccine failure were dug up from statements made many years ago and were simply recycled. Taken completely out of context, but slotted in to help the writer make their point. VERY bad journalism...

You will produce antibodies to just about anything that infects you (unless it kills you first, a la Ebola). I had assumed that the reader would take that as written. However, whether or not those antibodies help (measles) hinder (dengue) or do something in between (flu, RSV, rotavirus) depends on the pathogen and the immune target of the antibodies raised against it.

The denialists see things in a far more black and white way...which makes it easier to argue a point and still be kind of right, and yet at the same time horribly wrong. The "a priori" argument that antibodies are inactivating, therefore good, therefore proof of clearance of infection is simply wrong, as are many "a priori" arguments when faced with the real world. A phrase I use often is armchair science, when it's easier to perform a thought experiment that actually consider real data.

The confirmatory tests would probably be something like DNA or RNA PCR, or viral culture. A simple western blot would also be helpful in certain instances if the vaccine (any HIV vaccine) contains genes that aren't typically found in normal infection or is missing genes that are found in normal infection. The specifics would depend on the vaccine in question. I can recall at least one vaccine candidate that contained a marker gene but I don't think it got into large scale trials. The tests in this case seem to exclude a WB approach to weeding out vaccine-induced responses.

Without knowing the exact tests used at the trial site I can't be more specific, but there are plenty of options there. We do know that except in extremely rare instances HIV PCR and viral culture is very specific (meaning if you get a negative result, it's a true negative). They're not used so much for initial testing due to cost. I doubt that they'll use a commercial quantitative viral load assay though as they are not intended for confirmatory testing, it may be something in-house (hence the need to use a trial site, not any old testing center).

I hope that helps.


11:51 AM  
Blogger Moore said...

Dr. Bennett.

Ok, it was merely this categorically sounding formulation that caught my eye.

"The vaccine MrkAd5 HIV-1 is not supposed to produce anti-HIV antibodies".

I guess the meaning was that the main purpose of the vaccine was not production of HIV antibodies.

But still there are some confusing issues here. They halted the trials because they had too many HIV infections (true positives). I can't remember the number off the top of my head, but it was slightly more than the placebo group in one case. However, nowhere does it say how many (not necessarily undesirable) false-positives they got.

If they didn't get any false-positives, that would be rather strange and certainly a failure I'd imagine considering it was expected.

If, on the other hand, the vaccine stimulated both antibody response and CMI in large numbers of participants, it is equally strange that these people were not protected at all. Even if they were infected initially,one would have to assume that their immune reactions would be primed to immediately knock down the virus, thus giving the vacinees better hope of controlling the infection. But instead the researchers got extremey alarmed by something and dropped the whole thing.

12:49 PM  
Blogger Bennett said...

I don't have details on the true positives and how they distinguished them (culture, PCR, whatever) so can't comment much on whether or not they got false positives (meaning antibodies without infection, from our prior discussion). It would be nice to have that info.

I agree that it's disappointing that even with assumed CMI responses (which seem to be protective in the real world) this vaccine didn't help. The whole idea was as you say - to have some kind of pre-existing response to shut down early replication.

Any kind of preliminary data that shows that a study is failing will result in the study getting shut down - this is why interim analysis is performed, rather than waiting for several years for a result that they could have known about earlier on. Interim analysis allows people to detect toxicities or failures early on to avoid wasting time and money on a non-starter.

Personally, I think this approach had great merits, but no HIV vaccine has to date been effective. I had thought though that the reason was mostly because of attempts to purposefully induce antibody responses, whereas with this vaccine they were aiming specifically at CMI. In long-term-non-progressors and some multiply-exposed-but-uninfected people CMI appears to be extremely effective.

It's a sad tale of biology not cooperating with human manipulation... I don't know whether the magnitude of the responses was insufficient, or whether the immune target was wrong.

Vaccination inducing worse disease isn't a new phenomenon - a vaccine for respiratory syncitial virus in the mid 1960's was probably responsible for several deaths from RSV in vaccinated kids, whereas there were no deaths in the placebo group despite getting infected with RSV. The immune response to infection seemed to be greater if they were vaccinated, but just made the disease worse rather than better. This shut down RSV vaccine research for decades, and newer, safer options are still in early clinical trials even now.

7:37 PM  
Blogger Eugene Semon said...

You said, "And neither does the author of this article. The vaccine MrkAd5 HIV-1 is not supposed to produce anti-HIV antibodies"

Are you sure about this, Doctor Double?

There is also a role for the adeno part of this construct, is there not?

Here's what the designers say: "The study vaccine is designed to work by mimicking the shapes and structures of HIV."

Doesn't that mean antibody generation as a response?

3:10 PM  
Blogger Bennett said...

Gene - no, it does not. See my earlier posts on this point, which you probably haven't read. The most effective protection against HIV in most people seems to be cellular anti-HIV responses, not antibody anti-HIV responses. The same is true for most viruses, but in the case of HIV antibodies seem to do very little indeed.

The vaccine is intended to produce cellular antibody responses. It might produce antibody responses too, but that would be a side-effect, not the intended effect.


3:28 PM  
Blogger jtdeshong said...

I know this is an old thread, but I have been perusing this site, as I find Dr. Bennet very well informed and well written, as well as a great sense of humor.
I like the way you pointed out the antibody issue. When I first found out about HIV denialitsts, I was urged to watch a video titled something to the effect "10 Scientific Reasons HIV does not cause AIDS". The first thing my jaw hit the floor on, was Dr. Duesberg stating that HIV is harmless since the body forms antibodies to it. Dr. Duesberg went on to say that is the job of antibodies, to kill foreign invaders, and antibodies ALWAYS win! He said, "that is why you and I can sit here and hold this conversation." I am no doctor, but my science background does tell me that antibodies do NOT kill every foreign invader. If they did, then the Black Plague never would have happened. The flu pandemics we have had would never have killed so many people. Typhoid Mary would never have become famous. I could go on and on. It was just ludicruous that Dr. Dueschbag, er, I mean Duesberg could have even said that. Right then I knew he had an agenda of making blatantly false statements.
J. Todd DeShong

7:12 PM  

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