HIV-1 Tat-coated Nanoparticles - New Branch in Immunisation Technology

While going through my backlog of journals, I stumbled across a VERY interesting study in the journal Vaccine. Unfortunately, I have only a print subscription, not an online account, but I will provide the authors and date of publication at the end of the post for those of you intrepid enough to search out the full article for yourselves.

Basically, the study proposes that the the current vaccine research is heading in the wrong direction for reasons many scientists and doctors, including myself, agree with. Generally, HIV vaccines are created using the envelope of the virus. The only problem with this is that everytime the virus mutates, or everytime someone is coinfected with different subtypes or viral strains of HIV, it renders this vaccine useless. What this team is proposing, however, is that a vaccine be developed using the Tat protein in HIV. This protein is well conserved across subtype and viral strain lines, making it a good candidate for a general vaccine.

Some background: Tat is the transactivation protein responsible for HIV's ability to trigger a T-cell response, cause apoptosis in cells, and induce chemotactic receptor production in other WBCs that activate chemical signals necessary for the proliferation of HIV. What this new study shows is that when nanoparticles are coated with Tat protein and then injected into mice in varying doses, the mice would produce a humoral response to the protein. While the idea of using Tat isn't new, the idea of applying nanoparticle technology is. They compared their nanoparticle approach to the traditional protein-alum complex approach, and found that when using nanoparticles, it was possible to use as little as 1ug of nanoparticle-protein complex and still produce a humoral response. They also found that the response was reacting to the N-terminal and basic regions of the Tat protein, two of the most non-polymorphic areas of the protein, a major advantage.

In my opinion, this is HUGE. The fact that we can now produce a natural immune response to a common protein in all HIV lines in the most stable region of the protein is a key victory over this virus. If anyone has opinions or questions, please post them. I have a good deal of experience in HIV care management and clinical work, and would LOVE to have a real, civil discussion of HIV technology and care rather than doctor bashing. Thanks!

Oh, and here's the journal information for those who would like to purchase the article or try to find it via literature review:

Vaccine. Volume 24 (2006). "HIV-1 Tat-coated nanoparticles result in enhanced humoral immune responses and neutralizing antibodies compared to alum adjuvant". Patel, Jigna, David Galey, Julia Jones, et al. 3564-3573

I also meant to add in that this vaccine technology, that is, using nanoparticles coated in viral proteins, is much cheaper than the current attenuated virus technology as labs can constantly reproduce the protein and nanoparticles from one sample stock. It is also much safer as neither the protein nor the nanoparticles themselves can cause any sort of infection. The protein must be coupled with the live virus in order to have any affect, and the virus is never used in the vaccine process in this case.

Mariella

I am not really qualified to discuss the matter, but the article you quote can be viewed online at PubMed by the general public, or at least the citation can be.

I find it interesting that another article from 2004 is also listed Strong T cell type-1 immune responses to HIV-1 Tat (1-72) protein-coated nanoparticles
.

So I guess the one you wrote about is actually a followup on the original?

PS
Just because I am not qualified to discuss it does not mean I am not interested. Please continue posting about this so that we can learn more.

[edit on 7/12/06 by makeitso]

Yes, this is in fact a follow-up, good catch. The main difference in this one was that the team was looking at minimal possible dosage instead of just seeing if there was a reaction to protein coated nanoparticles.

Yes, the citation can be viewed on pubmed, the only downside is that only the abstract is available, that is, unless you subscribe to Vaccine, which unfortunately I don't subscribe to them online, just in print =(.

Another interesting point, however, is that a new drug just came out which is VERY promising for currently HIV+ patients. It's actually a combo drug, and is called Atripla. It is a combination of three current medications: tenofovir, emtricitabine, and efavirenz. These drugs, or at least the last two, are a common combination given in separate pills as they a re very hard to become resistant to. I think it's great that they combined these pills into a once-a-day dosage, as that makes it much more unlikely that patients will miss a dose.

Mariella

So what can the future study on this be, you say that scientists are heading in the wrong direction on creating a vaccine. Ever since i first heard that the hiv virus mutates at a very fast rate, and that there could be billions of possible strains i knew it would be hard to create a vaccine using conventional methods. But what you have said really intrigues me and i guess all i can say is thanks and i hope the vaccine goes well.

bsl4doc...

Thanks for the information. I don't know why my agency does not have a subscription to Vaccine, as I think it is an excellent resource to not only physicians but members of the general public.

I'm with you on this one, and it never dawned on me that Transactivating Regulatory proteins could be used in the development of a general vaccine to cover all the genetic mutations of HIV since it was first known about back in 1985. Because these particular proteins are essential for the viral replication process which leads to the conversion of virion RNA into DNA, I think as you, that this is one possible way to an effective vaccine. However, I have yet to see any effective drug trial for such a procedure, and in lieu of this, do you know of any further trials that were effectively done as the last one I heard about was back around 2002 when some Italian lab was going to start trials, or the one done with Rhesus monkeys that were immunized with the inactivated protein?

Also, I am not 100% convinced that an effective vaccine cannot be produced with proteins on the viral envelope or for that matter from REV, NEF, VPR, Group specific Antigens, or the like (to numerous to go over every one).

Originally posted by Jazzerman
bsl4doc...

Thanks for the information. I don't know why my agency does not have a subscription to Vaccine, as I think it is an excellent resource to not only physicians but members of the general public.

I'm with you on this one, and it never dawned on me that Transactivating Regulatory proteins could be used in the development of a general vaccine to cover all the genetic mutations of HIV since it was first known about back in 1985. Because these particular proteins are essential for the viral replication process which leads to the conversion of virion RNA into DNA, I think as you, that this is one possible way to an effective vaccine. However, I have yet to see any effective drug trial for such a procedure, and in lieu of this, do you know of any further trials that were effectively done as the last one I heard about was back around 2002 when some Italian lab was going to start trials, or the one done with Rhesus monkeys that were immunized with the inactivated protein?

Also, I am not 100% convinced that an effective vaccine cannot be produced with proteins on the viral envelope or for that matter from REV, NEF, VPR, Group specific Antigens, or the like (to numerous to go over every one).

Hello again!

Yes, there has been one trial that I know of in addition to the Italian lab. I can't recall where it was performed (it's the same lab that published this most recent paper), but they infected mice with HIV and allowed an infection to set up, and then vaccinated tham with Tat coated nanoparticles. They saw an incredible immune response, but had not determined if the infection was reversed, or simply combatted. We'll have to wait and see!

How long do you think it will take to establish if this will work, i heard scientist say that we are only a few years 5-10 years away from a vaccine...I hope they don't plan on continuing trying to create one using the viral dna.

What did the immune response look like in rats, also is it possible to transmit hiv into rats, i know that feline hiv cannot be transmitted to humans.

Originally posted by bsl4doc
Another interesting point, however, is that a new drug just came out which is VERY promising for currently HIV+ patients. It's actually a combo drug, and is called Atripla...I think it's great that they combined these pills into a once-a-day dosage, as that makes it much more unlikely that patients will miss a dose.

If only they could make a once-a-day pill like Atripla for the Entry Inhibitor Fuzeon, or any pill in conjunction with Fuzeon for that matter. It would also be lovely if someone could develop a medication without the side effects that the current medications have in some patients. Even Atripla has been know to cause serious mental problems, kidney problems, liver enlargement, Hep B flare ups, etc. One question...Have there ever been any known complications with Lipodystrophy from taking Atripla, as I know a few of the Nucleoside Reverse Transcriptase Inhibitors and a few Protease Inhibitors have this particularly visible side effect?

I also have hope that they will combine further medications to reduce the number of cocktails that patients take. Case in point, we have several HIV+ clients that are taking a once-a-day medication but end up taking 50 pills on top of the HIV medications to combat all the side effects from the HIV medications themselves. Now, I know that most any medications come with side effects of their own, but I really think researchers need to work hard to eliminate as many side effects from these medications as possible.

Originally posted by ATSGUY
How long do you think it will take to establish if this will work, i heard scientist say that we are only a few years 5-10 years away from a vaccine.

Sadly, I don't think we are going to see any sort of vaccination for HIV-1 or HIV-2 anytime soon. This is just my personal opinion, as I believe that most of the time and effort that is put into the medical side of the disease is heading down the road of "blocking" the virus, rather than "curing" the virus. There are certain labs and individuals that are actively researching and testing for a "cure" to HIV, but as bsl4doc originally stated...they may be heading down the wrong direction.

Only time will tell, but I wouldn't bet on it anytime soon.