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Author Topic: Scientists expose HIV weak spot  (Read 14934 times)

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Offline lostboy

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Scientists expose HIV weak spot
« on: February 14, 2007, 07:31:18 pm »
More good news:

http://news.bbc.co.uk/2/hi/health/6357287.stm



Scientists have shown what happens when an infection-fighting antibody attacks a gap in HIV's formidable defences.

The National Institute of Allergy and Infectious Diseases-led team say the work could aid HIV vaccine development.

They have published an atomic-level image in Nature showing the antibody, b12, attacking part of a protein on surface of the virus.

HIV avoids attack by constantly mutating, but this protein segment is a weak spot because it remains stable.

   
This is certainly one of the best leads to come along in recent years
Dr Gary Nabel,
National Institute of Allergy and Infectious Diseases

Dr Elias Zerhouni, director of the US National Institutes of Health (NIH), said: "Creating an HIV vaccine is one of the great scientific challenges of our time.

"NIH researchers and their colleagues have revealed a gap in HIV's armour and have thereby opened a new avenue to meeting that challenge."

Slippery foe

Developing a vaccine for HIV has proved extremely difficult.

The virus is able to mutate rapidly to avoid detection by the immune system, and is also swathed by a near-impenetrable cloak of sugary molecules which block access by antibodies.

But certain parts of the virus must remain relatively unchanged so that it can continue to bind to and enter human cells.

A protein, gp120, that juts out from the surface of the virus and binds to receptors on host cells, is one such region, making it a target for vaccine development.

Previous analysis of the blood of people who have been able to hold HIV at bay for long periods has revealed a rare of group of antibodies - including b12 - that seem to fight HIV with a degree of success.

The latest study has revealed the detailed structure of the complex, which is formed when b12 docks with gp120.

Until now this has proved impossible, because of the flexible nature of some of the chemical bonds involved.

But the NIAID team were able to stiffen up the key protein enough to capture a picture of the complex.

They hope that revealing the structure of this bond in such precise detail will provide clues about how best to attack HIV.

Challenge ahead

Researcher Dr Gary Nabel said the work had revealed a "critical area of vulnerability on the virus".

He said: "This is certainly one of the best leads to come along in recent years."

Keith Alcorn, editor of the aidsmap.com website, said vaccines based on antibodies had so far failed to produce promising results.

"These findings are very important because they show what sort of antibodies are likely to be most successful in neutralising HIV.

"Now the challenge is to develop vaccine products that can be tested in humans."

"There is no gene for the human spirit"

Offline Boo Radley

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Re: Scientists expose HIV weak spot
« Reply #1 on: February 14, 2007, 07:55:06 pm »
Sounds promising! 

Let's hope this finding makes it past all the tests and trials and comes out as a potent new agent to battle HIV.

Boo
String up every aristocrat!
Out with the priests and let them live on their fat!





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Offline marc11864

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Re: Scientists expose HIV weak spot
« Reply #2 on: February 14, 2007, 10:37:20 pm »
I just read about this in my RSS feed.

Not that a vaccine will be flying out to greet the public but this is still definitely good news.
Let us cavort like the Greeks of old! You know the ones I mean.

Offline bimazek

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Re: Scientists expose HIV weak spot
« Reply #3 on: February 15, 2007, 12:40:30 am »

this seems very very promising, with the shape, and the new facts, and the cd8 pd-1 connection, a therapudic vaccine should be possible, i hope with in 5-7 years, it is a big breakthrough
on many levels, one is the shape, another is the fact that it does not change and b12 is a vulnerability

Published online: 14 February 2007; | doi:10.1038/news070212-7
HIV reveals site of vulnerability
Potential vaccine target identified.

Medical researchers have found a chink in the constantly shape-shifting armour of the HIV virus. The discovery could be a significant step forward in the ongoing quest for a vaccine.

The AIDS virus evades the immune system because most of the proteins that cover the surface of the virus constantly change their structure. But researchers have now identified a site that doesn't change, and shown how an antibody can bind to it. If the body could be stimulated to produce its own copies of this antibody before infection, then in theory, it would allow it to attack the otherwise elusive virus and prevent infection.

"For a long time people have been asking whether an HIV vaccine is even possible," says Peter Kwong of the US National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, who led the research. "What this finding says is that it's not just a dream — there is this site of vulnerability."

Hide and seek

The discovery hinges on an HIV protein called gp120. During infection, gp120 latches onto a protein found in the human immune system called CD4. Because this is an essential step in the virus's replication cycle, a key site within gp120 retains its conformation, unlike other HIV surface proteins.

Vaccine researchers have known about this process for years, but there was a stumbling block. Previously, they thought that this site for antibody binding was hidden within the folds of the gp120 protein until the crucial moment of infection. This masking would mean that antibodies would not be able to recognize the unchanging portion and bind to it.

But Kwong and his colleagues have now shown that is not the case. This key part of gp120 are never hidden, they found — the protein doesn't change shape until after gp120 binds with CD4. This means that the never-changing binding site is not locked away from antibodies after all.

What's more, the team has succeeded in getting an antibody, called b12, to bind to gp120, and has studied the process to reveal the structure of the two molecules as they clamp together. They report their discovery in Nature1.

Mass production

The b12 antibody is already known to protect monkeys from infection with the related simian immunodeficiency virus. The challenge now lies in finding a way to get the human body to produce lots of b12 antibodies.

A vaccine could do this in several ways, says Kwong. It could be a protein or a string of DNA that gives the body information on how to produce b12. Or a part of the HIV gp120 protein could be used to stimulate the body to raise antibodies against it.

Some people infected with HIV have developed similar antibodies. But because they have already been exposed to the virus, it is too late to prevent permanent infection. So, such a vaccine would work only if given before infection.

The question, says Kwong, is whether a drug can be developed that stimulates antibody production in someone who has never encountered the virus. The researchers now plan animal tests to see whether high levels of the antibody can be achieved.

http://www3.niaid.nih.gov/news/newsreleases/2007/b12antibody.htm

http://scholar.google.com/scholar?hl=en&lr=&q=%22b12+antibody%22+hiv+gp120&btnG=Search

http://www.google.com/search?hl=en&q=Structural+definition+of+a+conserved+neutralization+epitope+on+HIV-1+gp120&btnG=Google+Search


Crystal Structure of a Neutralizing Human IgG Against HIV-1: A Template for Vaccine Design - group of 9 »
EO Saphire, PWHI Parren, R Pantophlet, MB Zwick, … - 2001 - sciencemag.org
... Antibody b12 recognizes the CD4-binding site of human immunodeficiency virus-1
(HIV-1) gp120 and is one of only two known antibodies against gp120 capable of ...


http://scholar.google.com/scholar?hl=en&lr=&q=%22b12+antibody%22+hiv+%22DNA%22&btnG=Search




Offline Miss Philicia

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Re: Scientists expose HIV weak spot
« Reply #4 on: February 15, 2007, 11:31:48 am »
This sounds more promising than a lot of the "oh whatever" things one often reads... but then I've been fooled before.
"I’ve slept with enough men to know that I’m not gay"

Offline robvaz123

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Re: Scientists expose HIV weak spot
« Reply #5 on: February 15, 2007, 11:32:29 am »
This doesn't sound anything like a theraputic vaccine.  At the end of the article they clearly state that it won't work to remove permanent infection.  Though I see how it may lead to an alternative treatment, I'm not sure I read anything that states that they are looking into a theraputic vaccine.  

This may prevent us from being a threat to other people by protecting them against further spread of infection.  And perhaps this approach will lead to new treatment options.  I do agree, however, that with the new gene therapy trials and the pd-1 connection, this may all tie into a non-toxic, easy to take, and extremely effective treatment protocol that will never fail.  Let's keep our fingers cross that the scientists and Pharma companies see the potential outside of a preventive vaccine.

Offline Optimistic

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Re: Scientists expose HIV weak spot
« Reply #6 on: February 15, 2007, 11:46:05 am »
Here's another article about it.

http://www.msnbc.msn.com/id/17156844/

Justin
12/06 (Atripla): cd4 - 260; cd% - 33%; vl - 169
1/07 (Atripla): cd4 - 267; cd% - 38.1%; vl - 132
4/07 (Atripla): cd4 - 373; cd% - 33.9%; vl - <50
7/07 (Atripla); cd4 - 287; cd% - 35.8%; vl - <50
9/07 (Atripla); cd4 - 356; cd% - 39.5%; vl - <50
12/07 (Atripla); cd4 - 517

Offline jupiter

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Re: Scientists expose HIV weak spot
« Reply #7 on: February 16, 2007, 02:30:02 am »

But certain parts of the virus must remain relatively unchanged so that it can continue to bind to and enter human cells.

A protein, gp120, that juts out from the surface of the virus and binds to receptors on host cells, is one such region, making it a target for vaccine development.


Well If they can target this part of the virus that doesnt change and mutate maybe they can focus on that point to cure the virus??

Offline J220

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Re: Scientists expose HIV weak spot
« Reply #8 on: February 16, 2007, 07:09:33 pm »
From what I understand I think that this has a greater potential to become a treatment method, one not subject to resistance, or even a preventive vaccine, but not a cure. From I gather this inhibits the virus from infecting cells, and thus may not do anything for already-infected cells. However, if this works as a new treament, it will probably make haart a thing of the past, and make hiv a permanently-latent infection. So although one would still be positive, the disease would never progress, and your immune system will not degrade. One the other hand, there is so much that is not known about the disease that who knows, maybe this will weaken the virus in the system so much that the body will be able to clear it out on its own. We'll have to wait and see!
"Hope is my philosophy
Just needs days in which to be
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Born on a New Day" - John David

Offline bimazek

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Re: Scientists expose HIV weak spot
« Reply #9 on: February 17, 2007, 09:42:57 pm »
if they can get a molecule to fit in this location then they can stimulate the natural human bodies immune system to suppress the virus every day with out or with less meds, probably completely with out meds, only with a therapuedic vaccine, i would say any vaccine that is discovered that can prevent will also have applications to treat and suppress the virus in humans, i believe that for many reasons in science, remember that many animals including 9% of all cats in usa, and monkeys and apes and chimps all get thier own version of hiv and never get sick because the virus is surpressed by natural immune system, the problem in human body is this exact new discovery finally after 25 years, they find how it masks and folds up and also the sugar coating on virus trick immune system (btw does anyone have any thoughts on this sugar coat and the blood ph or blood salt level, seems like a salty blood, or a high ph or low ph blood might effect that sugary coat on hiv and help to allow immune system to attack virus.)

so the deal is... the virus has vulnerabilities and other animals deal with it just fine, finally they have found the exact shape of one vulnerable point

see these science articles for more info...

remember any preventative vaccine will have therapudic abilities in my opinion because of these molecular geometry issues, the researches like to gain funding by talking about preventative vaccines because easier to get the moral non majority bush christians on board to "protect the innocent"  but i cannot imagine any case where a preventative vaccine would not have therapuedic abilities


http://forums.poz.com/index.php?topic=7475.0


http://www.google.com/search?hl=en&q=b12+gp120+hiv&btnG=Google+Search

Offline bimazek

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Re: Scientists expose HIV weak spot
« Reply #10 on: February 17, 2007, 10:26:16 pm »
Molecular features of the broadly neutralizing immunoglobulin G1 b12 required for recognition of human immunodeficiency virus type 1 gp120.

Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.

IgG1 b12 is a broadly neutralizing antibody against human immunodeficiency virus type 1 (HIV-1). The epitope recognized by b12 overlaps the CD4 receptor-binding site (CD4bs) on gp120 and has been a target for vaccine design. Determination of the three-dimensional structure of immunoglobulin G1 (IgG1) b12 allowed modeling of the b12-gp120 interaction in which the protruding third complementarity-determining region (CDR) of the heavy chain (H3) was crucial for antibody binding.

 In the present study, extensive mutational analysis of the antigen-binding site of Fab b12 was carried out to investigate the validity of the model and to identify residues important for gp120 recognition and, by inference, key to the anti-HIV-1 activity of IgG1 b12. In all, 50 mutations were tested: 40 in H3, 4 each in H2 and L1, and 2 in L3. The results suggest that the interaction of gp120 with H3 of b12 is crucially dependent not only on a Trp residue at the apex of the H3 loop but also on a number of residues at the base of the loop. The arrangement of these residues, including aromatic side chains and side chains that hydrogen bond across the base of the loop, may rigidify H3 for penetration of the recessed CD4-binding cavity. The results further emphasize the importance to gp120 binding of a Tyr residue at the apex of the H2 loop that forms a second finger-like structure and a number of Arg residues in L1 that form a positively charged, shelf-like structure. In general, the data are consistent with the b12-gp120 interaction model previously proposed. At the gene level, somatic mutation is seen to be crucial for the generation of many of the structural features described. The Fab b12 mutants were also tested against the b12 epitope-mimic peptide B2.1, and the reactivity profile had many similarities but also significant differences from that observed for gp120. The paratope map of b12 may facilitate the design of molecules that are able to elicit b12-like activities.


gp120
From Wikipedia, the free encyclopedia
Jump to: navigation, search

    The correct title of this article is gp120. The initial letter is shown capitalized due to technical restrictions.

gp120 is a glycoprotein exposed on the surface of the HIV envelope. The 120 in its name comes from its molecular weight of 120 kilodaltons.

The structure of gp120 involves an outer domain, an inner domain and a bridging sheet. The gp120 gene is around 1.5Kb long coding for around 500 amino acids. gp120 forms a sort of cap over the end of gp41 to make a gp120/gp41 subunit. This cap prevents the human immune response from recognising the virus via binding to gp41. However, when the virus needs to bind to a cell, the gp120 can change confirmation very quickly, exposing gp41.

The Human Immunodeficiency Virus (HIV) can mutate frequently to stay ahead of the immune system. There is however a highly conserved region in the virus genome that codes for structures to allow the virus to bind to a human cell and enter. The glycoprotein gp120 is anchored to the viral membrane through non-covalent bonds along with gp41, both coming from a cleaved protein, gp160. It infects any target cell with a CD4 receptor, particularly the helper T-cell, by binding to that receptor. Binding to CD4 is mainly electrostatic although there are van der Waals interactions and hydrogen bonds.

The exact mechanism of virus entry into a cell is unknown although the gp120 protein is thought to have at least responsibilities. It seeks out viable receptors on cells for virus entry, fixes the virus to the receptor on the cell and helps in passing the viral genome into the cell.

 gp120 vaccines

Since CD4 receptor binding is the most obvious step in HIV infection, gp120 was among the first targets of HIV vaccine research. These efforts have been hampered by the chemical and structural properties of gp120, which make it difficult for antibodies to bind to it; also, it can easily be shed from the virus' surface and captured by T-cells due to its loose binding with gp41. This has meant interest in using gp120 based HIV vaccine has been lost.



Antibody
From Wikipedia, the free encyclopedia

Schematic of antibody binding to an antigen

An antibody or immunoglobulin is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects like bacteria and viruses. Each antibody recognizes a specific antigen unique to its target.[1] This is because the two tips of the "Y" of the antibody contain a paratope (a structure analogous to a lock) that is specific for one particular epitope (analogous to a key) on an antigen, allowing these two structures to precisely bind together. This precise binding mechanism allows an antibody to tag a microbe or an infected cell for attack by other parts of the immune system, or to directly neutralize its target (i.e. by blocking a part of a microbe that is essential for its invasion and survival). The production of antibodies is the main function of the humoral immune system.[2]

Antibodies are soluble glycoproteins of the immunoglobulin superfamily.[3] The terms antibody and immunoglobulin are often used interchangeably. When attached to the surface of the B cell, the membrane-bound form of the immunoglobulin is sometimes referred to as the B cell receptor (BCR). Soluble antibodies are found in the blood and tissue fluids, as well as many secretions. In structure, they are globulins (in the ?-region of protein electrophoresis). They are synthesized and secreted by plasma cells that are derived from the B cells of the immune system.[4] Membrane-bound immunoglobulins are only found on the surface of B cells and facilitate the activation of these cells following binding of their specific antigen, and their subsequent differentiation into plasma cells for antibody generation, or memory cells that will remember the foreign antigen during future exposure. In most cases, interaction of the B cell with a T helper cell is necessary to produce full activation of the B cell and, therefore, antibody generation following antigen binding.[4]

In mammals there are five types of antibody: IgA, IgD, IgE, IgG, and IgM, with 4 IgG and 2 IgA subtypes present in humans (where Ig stands for immunoglobulin).[1] These are classified according to differences in their heavy chain constant domains (see below for more information regarding the structural features of antibodies).[3] Each immunoglobulin class differs in its biological properties and has evolved to deal with different antigens.

    * IgA can be found in areas containing mucus (e.g. in the gut, in the respiratory tract or in the urogenital tract) and prevents the colonization of mucosal areas by pathogens.[2]
    * IgD functions mainly as an antigen receptor on B cells.[2]
    * IgE binds to allergens and triggers histamine release from mast cells (the underlying mechanism of allergy) and also provides protection against helminths (worms).[2]
    * IgG (in its four forms) provides the majority of antibody-based immunity against invading pathogens.[2]
    * IgM is expressed on the surface of B cells and also in a secreted form with very high affinity for eliminating pathogens in the early stages of B cell mediated immunity (i.e. before there is sufficient IgG to do the job).[2]

Immature B cells express only IgM on their cell surface (this is the surface bound form, not the secreted form of immunoglobulin). Once the naive B cell reaches maturity, it can express both IgM and IgD on its surface - it is the co-expression of both these immunoglobulin isotypes that renders the B cell 'mature' and ready to respond to antigen.[1] Following engagement of the immunoglobulin molecule with an antigen, the B cell activates, and begins to divide and differentiate into an antibody producing cell (sometimes called a plasma cell). In this activated form, the B cell produces immunoglobulin in a secreted form rather than a membrane-bound form. Some of the daughter cells of the activated B cells undergo isotype switching, a mechanism by which the B cell begins to express the other Ig heavy chains and thus produce the IgD, IgA or (more commonly) IgG antibody isotypes.[1


"Targeted" monoclonal antibody therapy is already being employed in a number of diseases (including rheumatoid arthritis, multiple sclerosis and psoriasis) and in many forms of cancer including non-Hodgkin's lymphoma, colorectal cancer, head and neck cancer and breast cancer. Presently, many antibody-related therapies are undergoing extensive clinical trials for use in practice.[4]

Some immune deficiencies, such as X-linked agammaglobulinemia and hypogammaglobulinemia result in partial or complete lack of antibodies.[4] These diseases are often treated by inducing a short term form of immunity called passive immunity. Passive immunity is achieved through the transfer of readymade antibodies in the form of human or animal serum, pooled immunoglobulin or monoclonal antibodies, into the affected indvidual.[17]

Elevations in the different classes of immunoglobulins are sometimes useful in determining the cause of liver damage in patients whom the diagnosis is unclear:[3]

    * total IgA is elevated in alcoholic cirrhosis;
    * total IgM is elevated in viral hepatitis and primary biliary cirrhosis;
    * total IgG is elevated in viral hepatitis, autoimmune hepatitis and cirrhosis.




epitopes is the part of a macromolecule that is recognized by the immune system, specifically by antibodies, B cells, or cytotoxic T cells. Although epitopes are usually thought to be derived from nonself proteins, sequences derived from the host that can be recognized are also classified as epitopes.

Most epitopes recognized by antibodies or B cells can be thought of as three-dimensional surface features of an antigen molecule; these features fit precisely and thus bind to antibodies. The part of an antibody that recognizes the epitope is called a paratope. Exceptions are linear epitopes, which are determined by the amino acid sequence (the primary structure) rather than by the tertiary structure of a protein.

T cell epitopes are presented on the surface of an antigen-presenting cell, where they are bound to MHC molecules. T cell epitopes presented by MHC class I molecules are typically peptides between 8 and 11 amino acid in lengths, while MHC class II molecules present longer peptides, and non-classical MHC molecules also present non-peptidic epitopes such as glycolipids.

Epitopes can be mapped using protein microarrays, and with the ELISPOT or ELISA techniques.

Genetic sequences coding for epitopes that are recognised by common antibodies can be fused to genes, thus aiding further molecular characterization of the gene product. Common epitopes used for this purpose are c-myc, HA, FLAG, V5.

Interestingly, epitopes are sometimes cross-reactive. This property is exploited by the immune system in regulation by Anti-idiotypic antibodies (originally proposed by Nobel laureate Niels Kaj Jerne). If an antibody binds to an antigen's epitope, the paratope could become the epitope for another antibody that will then bind to it. If this second antibody is of IgM class, its binding can upregulate the immune response; if the second antibody is of IgG class, its binding can downregulate the immune response.

Intensive research is currently taking place to design reliable tools that will predict epitopes on proteins.

Offline Zanarkand

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Re: Scientists expose HIV weak spot
« Reply #11 on: March 03, 2007, 07:41:12 am »
This is what I can understand about it...

HIV hides in the body, HIV then infects white blood cells or something like it.
Your CD4 drops and Viral Load Increases.
Viral Load refers to the amount of HIV that has merged with your current blood.
CD4 Refers to how much blood is still healthy.

When someone takes HIV/ARV treatment etc...
When the Virus stops hiding (millions of cells at random times) it looks to infect a white blood cell.
The treatment prevents HIV from merging with the blood cell
When the White blood cell gets a chance to and undergoes Miosis or something to Duplicate itself, the amount of healthy CD4 cells increase.

If this new chemical agent destroys HIV when it emerges- HIV will never infect your blood even if you still have it hiding in your body.

Basically, HIV+ with no actual infection from the virus as explained happens in many Animals, ect.

Only unlike ARV's the agent can be manufactured by your body.
So it becomes a part of you and basically eliminates side effects that you would normally face from using a chemical based fighting agent (ARVS)

 ::) I'm no Genius but this doesn't seem like a PREVENTION method at all

Basically, if it is possible to get a human body to manufacture this agent naturally.
HIV will pretty much vanish....

Newbie to the Forum,
Zanarkand
All Your Base Are Belong To Us

Offline minus_25

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Re: Scientists expose HIV weak spot
« Reply #12 on: March 03, 2007, 09:32:40 am »
You sure do sound like a genius, Zanarkand!  My favorite line - "...undergoes Miosis or something to duplicate itself..."  LOL!

Btw, did you get the name, "Zanarkand" from FFX?

Offline Esquare

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Re: Scientists expose HIV weak spot
« Reply #13 on: March 03, 2007, 10:12:32 pm »


Basically, if it is possible to get a human body to manufacture this agent naturally.
HIV will pretty much vanish....


And thus become a non-factor if the treatment works if I am reading this right. If this could happen, while HIV would not be "cured", the stigma associated with the virus may go away to the point where those of us like me who are in secret about the virus would not have that worry that we have right now.

Offline Zanarkand

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Re: Scientists expose HIV weak spot
« Reply #14 on: March 04, 2007, 02:12:43 am »
Yeah Minus_25 :)
Final Fantasy teaches so many things.
At first when I discovered I was + Final Fantasy helped give me the strength to carry on at first.
In every Final Fantasy people give their lives. Yuna for instance was willing to sacrifice herself for the good of the people. That kind of ideology give me hope.
Today I'm not even worried about the virus. They say on average arvs add more than 35 years so I'm SO not even worried about it.
Then again, when before I knew that arvs would help that much- I still wasn't afraid cuz of FF :)

Imagine ARVS that replicate in your body with no side effects. I would imagine the only probelm would be what else does this antibody target? Assuming it only targets HIV's weakness. Brilliant
I think if this works out- for the first few weeks your Viral Load would become undetectable.
Afterwards your CD4 would increase. All without any medication. Natural Healing
It'll be impossible for your Viral Load to increase meaning the only Hiv left in the body would be hiding.
I would think that after a period of 3 years or so even all the latent infection of Hiv would cease.
The problem with current meds is that the Virus becomes immune while hiding.
So after a few months/years you have to swap over to new meds.

If the Viruses weak spot is that part which cannot mutate and become immune.
We've found that weakspot, and not in a drug! A living cell!

Anyways that's my 2c about what I think of this new weak spot.
Its the first time we have ever been able to actually destroy the virus without a sort of poison.
This means if they can replicate the antibody in humans naturally, well, I'll be quite happy :)
« Last Edit: March 04, 2007, 02:27:55 am by Zanarkand »
All Your Base Are Belong To Us

Offline HIVworker

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Re: Scientists expose HIV weak spot
« Reply #15 on: March 04, 2007, 06:15:51 pm »
In reading this thread I am a little confused as to where people are going with this. True, this new therapy might prevent HIV from getting into a cell. People have jumped from that to saying that it will prevent all new infections, thus clearing latent infection, decreasing viral load and other things that could eradicate the virus.

My question to these people is exactly how does this antibody differ from fuzeon - which does the same thing? The resistance profile of fuzeon is actually pretty good. In fact all antiretrovirals except protease inhibitors inhibit viral infection at some stage of the life cycle - which protect cells. Protease inhibitors prevent new viruses being infectious.

So I guess the question is how would a B12-like antibody be better than HAART? I don't believe that it would give people the ability to fight HIV like some animals do because that has been shown not to be due to a different antibody response.

I guess I am not clear what people are thinking here...

R
NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

Offline Zanarkand

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Re: Scientists expose HIV weak spot
« Reply #16 on: March 05, 2007, 12:01:41 pm »
Well, Fuzeon isn't a living cell. It runs out and expires.
If Fuzeon could destroy HIV and replicate in human bodies then we would have already had the cure for HIV.
Nuff said.
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Offline J220

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Re: Scientists expose HIV weak spot
« Reply #17 on: March 05, 2007, 04:00:15 pm »
In reading this thread I am a little confused as to where people are going with this. True, this new therapy might prevent HIV from getting into a cell. People have jumped from that to saying that it will prevent all new infections, thus clearing latent infection, decreasing viral load and other things that could eradicate the virus.

My question to these people is exactly how does this antibody differ from fuzeon - which does the same thing? The resistance profile of fuzeon is actually pretty good. In fact all antiretrovirals except protease inhibitors inhibit viral infection at some stage of the life cycle - which protect cells. Protease inhibitors prevent new viruses being infectious.

So I guess the question is how would a B12-like antibody be better than HAART? I don't believe that it would give people the ability to fight HIV like some animals do because that has been shown not to be due to a different antibody response.

I guess I am not clear what people are thinking here...

R

The article mentions the possibility of this discovery assisting in the development of a vaccine, not as a drug...if you can elicit a response to create b12 on its own then this can make haart obsolete. Fuzeon, on the other hand must be taken daily. Let's see, what is better, a vaccine that makes the body control the infection effectively by itself, or taking drugs or shots daily, with side effects???
« Last Edit: March 05, 2007, 06:35:08 pm by J220 »
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Born on a New Day" - John David

Offline HIVworker

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Re: Scientists expose HIV weak spot
« Reply #18 on: March 05, 2007, 08:03:15 pm »
I guess my point is that if viral entry was such a good thing then fuzeon WOULD have been the cure and it wasn't. I understand the vaccine potential of this study, but for an existing infection I don't see any benefit over fuzeon because even if the body could make a B12 like antibody, it wouldn't cure the virus. It would have fewer side effects, but it wouldn't be the cure that some on this thread think it might be.

R
NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

Offline J220

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Re: Scientists expose HIV weak spot
« Reply #19 on: March 05, 2007, 09:06:30 pm »
Oh no question about it R., this is not what I would call a "cure" candidate, but this would have huge positive impact for those who have to inject themselves with fuzeon twice a day! On that score alone, regardless of whether this particular mechanism is not the best target, this is what I would consider a huge benefit. Regards, J.
« Last Edit: March 05, 2007, 09:09:21 pm by J220 »
"Hope is my philosophy
Just needs days in which to be
Love of Life means hope for me
Born on a New Day" - John David

Offline Zanarkand

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Re: Scientists expose HIV weak spot
« Reply #20 on: March 07, 2007, 10:25:36 am »
Personally, I think the meaning of "Cure" is to suffer no effects from the virus without the need of any drug.
If that became the case then we would be no different from hiv- people.
No Meds, No Drugs, No Side Effects, No Resistances, No Signs, No Low CD4, No Viral Load.
However if someone manages to get the virus from you, they'd need a similar vaccine.
How is this not a cure?
Please expand because I don't really understand what you're trying to say  ::)
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Offline J220

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Re: Scientists expose HIV weak spot
« Reply #21 on: March 07, 2007, 10:34:54 am »
Well, a true "cure" in the clinical sense, means complete the elimination of the pathogen from the body, along with all manifestations and physical consequences. Then there's what you just described, which would be just as absolutely fantastic, and what I suspect is very close to happening given so many therapy candidates. The priority for all of us is indeed a non-med, long-lasting, not susceptible to resistance therapy that will make the virus something that' is just "there" but never progresses nor affects us in any way. But to be accurate, and from a matter of definition of semantics, cure is what I wrote above (at least how I understand it!). But again, if this discovery leads to a therapy like you  mentioned, or the VX496, or the rybozyme, then that would have great benefits! Regards, J.
"Hope is my philosophy
Just needs days in which to be
Love of Life means hope for me
Born on a New Day" - John David

Offline Zanarkand

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Re: Scientists expose HIV weak spot
« Reply #22 on: March 07, 2007, 10:44:22 am »
True, True!  ;)
But if you think about it, we have millions of viruses in our bodies at any given time.
The aim is to reduce HIV to something similar to Chicken-Pox.
As is- Today HIV is more along the class of Diabetes
Things are looking up people!

Hugs to Everyone,
Kent
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Offline HIVworker

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Re: Scientists expose HIV weak spot
« Reply #23 on: March 07, 2007, 11:41:42 am »
I'm not sure I would class HIV as being like diabetes. See the LIVING section as to why, this is currently a topic under discussion. My own view is that we want to eradicate HIV and not turn it into some chronic more benign infection. Having it be like diabetes would be a step forward, but it isn't where the field should go. That's stopping short of a desired goal.

R
NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

Offline Zanarkand

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Re: Scientists expose HIV weak spot
« Reply #24 on: March 07, 2007, 11:46:48 am »
True, but any improvements are better than none
Still, I see what you mean.
The moment it becomes reduced to that the amount of people working on a cure will sink into nothingness
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Offline bimazek

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Re: Scientists expose HIV weak spot
« Reply #25 on: March 22, 2007, 03:42:36 am »

WSU alumni play major role in HIV breakthrough

Hope for vaccine bolstered

Drs. Tongqing Zhou and Barna Dey, both Wayne State alumni,
played major roles in the recent HIV-AIDS discovery.
The computer screen shows the HIV gp120:b12 structure.

Former Wayne State graduates, Drs. Tongqing Zhou and Barna Dey, played a major role in the recent HIV-AIDS discovery made at the Vaccines Research Center at the National Institute of Allergy and Infectious Diseases (NIAID). The discovery was featured in the February 15, 2007 issue of Nature, a journal that publishes articles on a wide range of issues relating to science and technology.

Dey received her Ph.D. from the Department of Biochemistry and Molecular Biology at WSU’s School of Medicine. Unfortunately, she was out of the country and unavailable for comment.

Zhou graduated from the Chinese Academy of Sciences in 1994 with a Ph.D. in cell biology, then traveled to the U.S. to be a postdoctoral associate under Dr. Barry Rosen, chair of Wayne State’s Department of Biochemistry and Molecular Biology, where he stayed until 2001.

He left to work for the National Institute of Health (NIH.) Zhou received a master’s degree in computer engineering from WSU’s College of Engineering.

The research, which lead to this discovery, under the leadership of the study’s lead author, Dr. Peter Kwong from NIAID, involved finding, then mapping a small piece of the HIV virus’ outer coat that could be critical in finding a vaccine against this virus that thus far has proven to be incurable.

According to a press release from Wayne State’s Medical School, the aim of the study was to target a particular point on the virus’ gp120 surface protein, which appears to not mutate between strands and binds to an antibody that is already found in some humans, according to the research team. The nature of the outer coating makes finding a vaccine very difficult because mutations occur frequently.

“The trick has been to find a spot that stays the same between different strains and can also be accessed by antibodies that humans could produce in large numbers,” Kwong said.

The researchers were able to do this by making atomic level images of the virus, using X-ray crystallography, which revealed the structure of the protein, gp120, while it was bound to an infection fighting antibody, b12.

Kwong and his colleagues at NIH published the first X-ray snapshot of the core of HIV gp120 as it attached to a cellular receptor known as CD4 in 1998. The CD4 receptor site on human T cells is the attachment point where the HIV virus invades human cells.

Zhou said, via email, that by using X-ray crystallography, surface-plasmon resonance characterization and structure-assisted conformational stabilization of proteins and the 3-dimentional structural information established by Dr. Kwong in 1998, the research team was able to computationally design and experimentally introduced mutational changes into the gp120 proteins, hoping to stabilize them into the CD4-bound shape.

The changes were confirmed by x-ray crystallography. The detailed gp120-b12 antibody structure presented in the paper was obtained by first crystallizing together one of the designed gp120 complexed with the b12 antibody.

They then radiated the crystals with a special X-ray source to obtain the diffraction patterns. Subsequent computational transformations visualized a detailed snapshot — a broadly neutralizing antibody attacking the HIV gp120 protein at the same point where gp120 initially attaches to the CD4 receptor.

Since the gp120 protein is how the virus gains entry to the human cell, finding an antibody (b12) that can be produced by humans that can block this process is exactly what they were aiming for. Even better, the researchers have discovered that this b12/gp120 connection does not change its configuration regardless of what strain of the virus it is found on.

What this means is that the researchers may have found a “site of vulnerability” that vaccines may be designed to target someday.

Does that mean that they have cured AIDS?

No.

It does, however, mean that they have made an enormous breakthrough.

The next stage is to do research to see if the antibodies can be produced in animals.

“It’s hard to see from this point, (when a vaccine might be available,) we cannot predict,” Zhou said, “This information gave us a target. This kind of information is going to guide us to do a rational design, for a working antibody, how a working antibody works, how a neutralizing antibody attacks.

“This time it’s a very big step forward, optimistically we’re 10 years away.”

Zhou said that his master’s degree in computer engineering has helped him in the field of structural biology due to the frequent use of computer imaging in the lab.

While working under Rosen at WSU, Zhou’s research was mainly focused on metal resistance in bacteria. Studying the biochemical characteristics of the arsenic pump, he became interested in structural biology, hoping to understand the mechanisms from another aspect.

Under the tutelage of Dr. Domenico Gatti, Zhou successfully crystallized and solved the structure of the ArsA protein, the catalytic subunit of the arsenic pump. This research on how the e.coli bacterial cells are able to pump toxic arsenic out of its cells has implications in studies involving how tumor cells react to chemotherapy.

His work in structural biology made him realize the importance of honing his computer skills.

“I started at the Engineering Computer Center (ECC) around 1998,” Zhou said, “I needed computer skills that would help me in the field of structural biology. A combination of biology, computers and physics helped me to get this position (at NIAID.)”

Working at the ECC gave Zhou the needed skills in programming, operating systems and database management.

The status and importance of this research reflects very well on WSU’s Medical School.

In an interview conducted via email, Rosen discussed the impact this will have on the school.

“It demonstrates how determining the structure of disease proteins brings basic sciences to clinical medicine and human health,” Rosen said, “When prospective medical and graduate students learn of the quality of our graduate and research programs, and, in particular, the strength of?the department of biochemistry and molecular biology in structural biology and molecular biophysics, the medical school and our department will get higher quality students.”

Rosen first met Zhou while collaborating with Zhou’s advisor in Beijing.

“In Beijing Dr. Zhou was my teacher and guide, showing me how to do advanced fluorescence spectroscopy as well as the sites  of Beijing,” Rosen said.

He and his advisor then visited my lab for a summer.

“After he received his Ph.D., he joined my lab as a postdoctoral research associate and learned both structural biology and computer science.

“These skills led to his present position at NIH, where he is now doing world-class structural biology with HIV.”



Offline hahaha

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Re: Scientists expose HIV weak spot
« Reply #26 on: March 22, 2007, 11:31:15 pm »

Does that mean that they have cured AIDS?

No.

It does, however, mean that they have made an enormous breakthrough.

The next stage is to do research to see if the antibodies can be produced in animals.

“It’s hard to see from this point, (when a vaccine might be available,) we cannot predict,” Zhou said, “This information gave us a target. This kind of information is going to guide us to do a rational design, for a working antibody, how a working antibody works, how a neutralizing antibody attacks.

“This time it’s a very big step forward, optimistically we’re 10 years away.”

10 years!!!!, I may die already and have only bones left on the ground......
I sometimes wonder, why ever research have to go thru this mice-->rabbit-->simian-->human.  Can they just skip one or two steps?  Especially if the test on rabbit is successful, then science have to make a "purchase order" on the simian (like order a product), after the receipt of the purchase order, the "manufacturer" then grow the simian, which take for ages to grow......

don' they know people are dying because there is no cure?.....Can't they just raise more Simian and have "stock" in their "warehouse"?

I feel effortless sometimes.....
Aug 9, 2006 Get infected in Japan #$%^*
Oct 2006 CD4 239
Nov 2006 CD4 299 VL 60,000
Dec 1, Sustiva, Ziagan and 3TC
Jan 07, CD4 400

 


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