Confessions of a Subversive Grad. Student: "More" Vaccine Politics

AIDS Inc. has created a loose-cannon monster, aka “Burton’s Frankenstein”, in the one and only John P Moore, who is becoming the AIDS establishment’s least favorite mistake. Moore’s grave error --  making AIDS dissidents a public issue that will not go away, has struck the nerves of some of the biggest names in HIV/AIDS science. Some AIDS giants are even suggesting that the Moore error is the reason for the recent change of direction in HIV immunology/vaccine research. 

At the Toronto 2006 AIDS show, Anthony Fauci claimed that the recent shift in funding was the result of issues too complicated to explain in the time allotted. These issues were said to be concerns related to a 2005 Science publication by a group headed by Barton F Haynes. While Haynes’ observations and conclusions are of much interest, they are far from unquestionable, and are therefore very unlikely to be the sole reason for the shifts in the funding tide I wrote about on Monday.

To appreciate the above, it is necessary to understand the Hayes’ paper a little, so let me try and explain. Haynes et al. tested the reactivity of a set of “broadly neutralizing” HIV antibodies against an array of natural components of the human body, such as cardiolipin and DNA. They showed that some of these HIV antibodies were reactive with the self-molecules. Following these observations, the Haynes’ group and Gary Nabel claimed the autoreactivity of these antibodies may be responsible for the lack of success researchers have had with inducing these antibodies through vaccination. A quick read through the article, and other literature in the area, demonstrate that policy/funding was not changed solely because of this publication. 

First, Haynes’/Nabel’s conclusion that these broadly neutralizing antibodies would not get through the tolerance process, of the development of B lymphocytes, is flawed. The researchers used antibodies produced by mature and/or memory B cells. These cells have already gone through a rapid phase of mutation known as somatic hypermutation. The occurrence of somatic hypermutation (i.e., a rapid rearrangement of immunoglobulin V(D)J genes – V(D)J genes are explained in this primer from PLOS Medicine), in antibody secreting cells, acts to increase the affinity of the antibodies for their molecular targets. The antibodies that were used in the Haynes et al. study were initially produced by cells that had already gone through this process. There is no guarantee, therefore, that these antibodies were indeed autoreactive before their genes had gone through the somatic hypermutation process. The autoreactivity of these antibodies could have been a result of the mutational changes that occurred during the B lymphocyte development. If this is the case, these antibodies would not be had been prevented from developing further during the tolerance process, and the Haynes’ conclusion would be false. This possibility, however, has not been investigated, although it is quite obvious.

Second, Haynes et al. cited a paper from Michael Nussenzweig’s lab (This is not the one cited, but it contains the relevant data) as evidence of broadly neutralizing HIV antibodies sharing certain characteristics with autoreactive antibodies. This comparison was also flawed. The Nussenzweig paper discussed the characteristics of autoreactive antibodies that are eliminated during the tolerance process. There are no guarantees that these autoreactive antibodies have the same characteristics as the “mature” autoreactive antibodies found in patients with autoimmune disorders (such as systemic lupus). An actual valid comparison has also never been completed.

Third, Alexandra Trkola’s group, at the University Hospital of Zurich, published, in 2005, an article describing the use of these broadly neutralizing HIV antibodies in passive immunological therapy of HIV infection. The article explained no adverse side-effects that resembled the presence of autoreactive antibodies. 

It is more than clear, therefore, that the Haynes et al. conclusion is less than super-substantial. Why then would funding decisions be changed solely because of it?

My talks with prominent AIDS researchers suggest that the Haynes publication has had very little to do with these changes. Members of the Burton lab have told me that the backlash experienced by Burton, in terms of not receiving any of the prestigious Gates’ money, is AIDS Inc.’s way of punishing Moore.

A senior colleague shared the same sentiment. This researcher, a recipient of multiple NIH grants, said that Burton needed to detach himself from Moore, and was of the opinion that “Fauci had his head up Haynes’ ass” for two reasons. It provided an excuse as to why there was no HIV vaccine. Second, it was a mechanism for Fauci to punish Moore and those who made him. This colleague, a self-conceived AIDS deity, has long been associated with Burton. The investigator now blames disappearing funding on the  long-standing relationship. But be clear Dennis Burton is not the goat. It is Moore who is held in contempt and blamed. 

I find it more than strange that Alexandra Trkola’s work, which is the main piece of evidence against Haynes et al., is being ignored. One look at Dr. Trkola’s website reveals her main collaborators. Is it a coincidence that “Burton's Frankenstein” is on the list?

Grad. Student studies B-cell immunology at a well known university that is not in Australia.

Comments

[Chris Tyler]

I think this paper, 'Cardiolipin polyspecific autoreactivity in two broadly neutralizing HIV-1 antibodies' mentioned above, is troubling for the reason specified (inducing autoantibodies), but what I see is something more fundamental.

Antibodies are used so flippantly in 'HIV' research, testing, and science that people have forgotten a very fundamental caveat they come with; even MONOCLONAL antibodies are POLYSPECIFIC.

"Here we demonstrate that the two most broadly reactive HIV-1 envelope gp41 human mAbs, 2F5 and 4E10, are polyspecific autoantibodies reactive with the phospholipid cardiolipin."

The problem is that any time a reaction is seen on the 'HIV' antibody tests, the assumption is made that it's 'HIV' antibodies reacting; and that there are even such things as 'HIV' antibodies to begin with.

The Perth Group have repeatedly pointed out that even monoclonal antibodies are polyspecific and as such can be complete wild-cards. This is especially important with tests like the p24 antigen test which claims to use monoclonal antibodies to p24. Since it's known that the p24 antigen test is just a tad less than reliable, it's a wonder so many people go on using antibodies, even 'monoclonal' antibodies, to base not only diagnostic decisions upon but also so much research.

Given the fact that so many people who do end up testing positive have had a history of broad antigenic stimulation, it's a wonder why the claim is made that the 'HIV' antibodies are 99.9% accurate given the chaotic history many serum samples have been through.

For me the paper above round-aboutly demonstrates that sure, vaccine development is dicey at best, but more fundamentally, antibodies they so preciously rely on are an even more dicey foundation for 'HIV' science to rest so much of its weight on.

Chris

[Michelle Thomas]

Those "rare broad HIV-neutralizing polyspecific abs" may owe their efficacy solely to the exposed host cell phospholipids, and not any viral epitopes.

- and that may not be a bad thing...

google "bavituximab"

MT

[Subversive Grad. Student]

Michelle

The antibody you mention, Bavituximab, is a laboratory developed antibody, which has nothing to do with the broadly neutralizing anti-HIV antibodies 2F5, 4E10, and 2G12. Bavituximab was designed to be used for passive treatment of individuals infected with viruses, or afflicted by cancer. Also, the developers of this monoclonal antibody (Mab), Peregrine Pharmaceuticals, have no desires to induce this antibody through vaccination.
Researchers of the broadly neutralizing anti-HIV antibodies (i.e., 2F5, 4E10, & 2G12), however, do have an intent to induce these antibodies through vaccination. This process is potentially dangerous, especially if these antibodies are, as Haynes et al. suggested, autoreactive. Messing with immunological tolerance would not only open the doors for production of these anti-HIV antibodies, it could potentially allow the production of a variety of other autoreactive antibodies.

GS

Note from Otis: MT, You will have noticed that two comments of yours subsequent to the one replied to here have been deleted. The reason is quite simply that GS's essays were not intended to open a discussion of immuno-babble suitable for specialists (even if they claim to be "lay people"). Your point has been addressed quite fully once. If you wish to enjoy any further correspondence and edification from GS, send him an email through me.