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Author Topic: Two naturally occurring antibodies discovered  (Read 6288 times)

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Offline Cosmicdancer

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Two naturally occurring antibodies discovered
« on: July 08, 2010, 03:18:16 PM »
Scientists discovered two naturally occurring broadly neutralizing antibodies (VRC01 and VRC02) that neutralize more strains of HIV than any previously discovered antibodies.  This may help accelerate design of an effective vaccine, according to researchers.

http://www.sciencedaily.com/releases/2010/07/100708141531.htm

Antibodies found that prevent most HIV strains from infecting human cells

Scientists have discovered two potent human antibodies that can stop more than 90 percent of known global HIV strains from infecting human cells in the laboratory, and have demonstrated how one of these disease-fighting proteins accomplishes this feat. According to the scientists, these antibodies could be used to design improved HIV vaccines, or could be further developed to prevent or treat HIV infection. Moreover, the method used to find these antibodies could be applied to isolate therapeutic antibodies for other infectious diseases as well.

"The discovery of these exceptionally broadly neutralizing antibodies to HIV and the structural analysis that explains how they work are exciting advances that will accelerate our efforts to find a preventive HIV vaccine for global use," says Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health. "In addition, the technique the teams used to find the new antibodies represents a novel strategy that could be applied to vaccine design for many other infectious diseases."

Led by a team from the NIAID Vaccine Research Center (VRC), the scientists found two naturally occurring, powerful antibodies called VRC01 and VRC02 in an HIV-infected individual's blood. They found the antibodies using a novel molecular device they developed that homes in on the specific cells that make antibodies against HIV. The device is an HIV protein that the scientists modified so it would react only with antibodies specific to the site where the virus binds to cells it infects.

The scientists found that VRC01 and VRC02 neutralize more HIV strains with greater overall strength than previously known antibodies to the virus.

The researchers also determined the atomic-level structure of VRC01 when it is attaching to HIV. This has enabled the team to define how the antibody works and to precisely locate where it attaches to the virus. With this knowledge, they have begun to design components of a candidate vaccine that could teach the human immune system to make antibodies similar to VRC01 that might prevent infection by the vast majority of HIV strains worldwide.

NIAID scientists Peter D. Kwong, Ph.D., John R. Mascola, M.D., and Gary J. Nabel, M.D., Ph.D., led the two research teams. A pair of articles about these findings appears in the online edition of Science.

"We have used our knowledge of the structure of a virus -- in this case, the outer surface of HIV -- to refine molecular tools that pinpoint the vulnerable spot on the virus and guide us to antibodies that attach to this spot, blocking the virus from infecting cells," explains Dr. Nabel, the VRC director.

Finding individual antibodies that can neutralize HIV strains anywhere in the world has been difficult because the virus continuously changes its surface proteins to evade recognition by the immune system. As a consequence of these changes, an enormous number of HIV variants exist worldwide. Even so, scientists have identified a few areas on HIV's surface that remain nearly constant across all variants. One such area, located on the surface spikes used by HIV to attach to immune system cells and infect them, is called the CD4 binding site. VRC01 and VRC02 block HIV infection by attaching to the CD4 binding site, preventing the virus from latching onto immune cells.

"The antibodies attach to a virtually unchanging part of the virus, and this explains why they can neutralize such an extraordinary range of HIV strains," says Dr. Mascola, the deputy director of the VRC.

With these antibodies in hand, a team led by Dr. Kwong, chief of the structural biology section at the VRC, determined the atomic-level molecular structure of VRC01 when attached to the CD4 binding site. They then examined this structure in light of natural antibody development to ascertain the steps that would be needed to elicit a VRC01-like antibody through vaccination.

Antibody development begins with the mixing of genes into new combinations within the immune cells that make antibodies. Examination of the structure of VRC01 attached to HIV suggested that, from a genetic standpoint, the immune system likely could produce VRC01 precursors readily. The researchers also confirmed that VRC01 does not bind to human cells -- a characteristic that might otherwise lead to its elimination during immune development, a natural mechanism the body employs to prevent autoimmune disease.

In the final stage of antibody development, antibody-producing B cells recognize specific parts of a pathogen and then mutate, or mature, so the antibody can bind to the pathogen more firmly. VRC01 precursors do not bind tightly to HIV, but rather mature extensively into more powerfully neutralizing forms. This extensive antibody maturation presents a challenge for vaccine design. In their paper, Dr. Kwong and colleagues explore how this challenge might be addressed by designing vaccine components that could guide the immune system through this stepwise maturation process and facilitate the generation of a VRC01-like antibody from its precursors. The scientists currently are performing research to identify these components.

The discoveries we have made may overcome the limitations that have long stymied antibody-based HIV vaccine design," says Dr. Kwong.

The two research teams included NIAID scientists from the VRC, the Laboratory of Immunoregulation, and the Division of Clinical Research, all in Bethesda, Md.; as well as researchers from Beth Israel Deaconess Medical Center in Boston; Columbia University in New York; Harvard Medical School and Harvard School of Public Health in Boston; The Rockefeller University in New York City; and University of Washington in Seattle.
Summer, 2007 - &$#@?
November, 2007 - Tested poz, 300,000 vl, 560 cd4
Feb, 2008 - 57,000 vl, 520 cd4, started Atripla
June, 2008 - undetectable, 612 cd4
January, 2009 - undetectable, 670 cd4
May, 2009 - undetectable, 593 cd4
Sept, 2009 - 83 vl, 763 cd4, 34%
Dec, 2009 - undetectable, 889 cd4, 32%
April, 2010 - undetectable, 860 cd4, 31%
October, 2010 - undetectable, 800 cd4, 38%
April, 2011 - undetectable, t-cell test not done
October, 2011 - undetectable
April, 2012 - undetectable, 850 cd4, 39%
November, 2012 - undetectable, 901 cd4, 41%
April, 2013 - undetectable, 846 cd4, 36%
October, 2013 - undetectable

Offline Inchlingblue

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Re: Two naturally occurring antibodies discovered
« Reply #1 on: July 08, 2010, 04:20:12 PM »
This is similar to another recent discovery of two other broadly neutralizing antibodies.

LINK:

http://forums.poz.com/index.php?topic=28801.0

Offline esper

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Re: Two naturally occurring antibodies discovered
« Reply #2 on: July 08, 2010, 08:11:35 PM »
Also front page news on the WSJ, which mentions some related, unpublished work as well. nice news to start the day with!

http://online.wsj.com/article/SB10001424052748703609004575355072271264394.html?mod=WSJASIA_hpp_MIDDLETopStories
tested positive June 26, 2009
06/26/2009-CD4 428: VL 56,200: 34.1%
09/28/2009-CD4 388: VL 105,000: 31.9%
11/16/2009-CD4 330: VL 242,000: 23.4%
12/11/09 started stocrin (sustiva) & truvada
02/02/2010-CD4 588: VL 204: 31.6%
04/27/2010-CD4 620; VL 154; 38.5%
08/25/2010-CD4 504; VL undet; 39.2%
11/16/2010-CD4 499: VL undet: 44.6%
03/01/2011-CD4 534: VL undet: 33.2%
06/01/2011-CD4 709: VL undet: 45.6%
12/11/2011-CD4 537: VL undet: 41.5%
06/10/2012-CD4 597: VL undet: 42.8%

Offline J220

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Re: Two naturally occurring antibodies discovered
« Reply #3 on: July 09, 2010, 12:24:28 AM »
Great, great news....could the end really be in sight?

Fox news carried it as well....

http://www.foxnews.com/story/0,2933,596242,00.html?test=latestnews
"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 veritas

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Re: Two naturally occurring antibodies discovered
« Reply #4 on: July 09, 2010, 05:36:56 AM »


Now the trick is, to get the body to manufacture these antibodies. VRCO 1 does not bind to human cells( but it does attach to the virus) so this might lead to  elimination by the body and loss of efficacy. However,if the body could manufacture the antibodies.......

Nice find

v

Offline veritas

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Re: Two naturally occurring antibodies discovered
« Reply #5 on: July 09, 2010, 09:26:34 AM »

More on these fabulous antibodies and the immune system:

"These proteins produced by the innate immune system are crucial for creating a preventive vaccine, and could also have therapeutic uses developed in the coming years or decades."


http://www.scientificamerican.com/article.cfm?id=discovery-of-new-antibodies-hiv

It seems as though adaptive immunity is crucial (sound familiar?).

v

Offline Inchlingblue

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Re: Two naturally occurring antibodies discovered
« Reply #6 on: July 09, 2010, 11:44:31 AM »
I thought it was interesting that when they were looking for these antibodies they did not look at elite controllers:

Researchers at NIH Vaccine Research Center (VRC) decided to look at neutralizing antibodies in the blood of persons who are able to better control HIV infection. Elite controllers were not part of the mix because they seem to control HIV through their adaptive immunological system T cell mechanisms.


LINK:

http://www.scientificamerican.com/article.cfm?id=discovery-of-new-antibodies-hiv

Offline tennisplayer56

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Re: Two naturally occurring antibodies discovered
« Reply #7 on: July 09, 2010, 12:04:15 PM »
More on these fabulous antibodies and the immune system:

"These proteins produced by the innate immune system are crucial for creating a preventive vaccine, and could also have therapeutic uses developed in the coming years or decades."


http://www.scientificamerican.com/article.cfm?id=discovery-of-new-antibodies-hiv

It seems as though adaptive immunity is crucial (sound familiar?).

v

I'm confused. Aren't antibodies part of your adaptive immunity?

Offline veritas

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Re: Two naturally occurring antibodies discovered
« Reply #8 on: July 09, 2010, 01:55:06 PM »

tennisplayer56,

You said: "I'm confused. Aren't antibodies part of your adaptive immunity?"

Yes, they are! However, not all antibodies are manufactured by your immune system.If they were, we would have the same immunity as the person who was found to have VRCO1 and 2. Also, your immune system might not produce the antibodies in sufficient numbers to do any good. Thus, you immune system has to be helped. If you could teach your immune system to manufacture these antibodies, you have a functional cure.

v

Offline tennisplayer56

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Re: Two naturally occurring antibodies discovered
« Reply #9 on: July 09, 2010, 04:41:40 PM »
tennisplayer56,

You said: "I'm confused. Aren't antibodies part of your adaptive immunity?"

However, not all antibodies are manufactured by your immune system.If they were, we would have the same immunity as the person who was found to have VRCO1 and 2. Also, your immune system might not produce the antibodies in sufficient numbers to do any good. Thus, you immune system has to be helped. If you could teach your immune system to manufacture these antibodies, you have a functional cure.

v

Thanks. But im confused again. I thought all antibodies were produced by your immune system. Are you saying that this person with the VRCo1/2 received those antibodies in some other way? (ie maternal transmission).
Also, when you say functional cure, are these antibodies (or antibodies in general) able to attack the latent reservoirs? I thought a functional cure could only be achieved (theoretically) reactivating those reservoirs.

Sorry for the questions
Thanks =) This stuff is pretty interesting to me.

Offline veritas

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Re: Two naturally occurring antibodies discovered
« Reply #10 on: July 09, 2010, 05:11:36 PM »
Thanks. But im confused again. I thought all antibodies were produced by your immune system. Are you saying that this person with the VRCo1/2 received those antibodies in some other way? (ie maternal transmission).
Also, when you say functional cure, are these antibodies (or antibodies in general) able to attack the latent reservoirs? I thought a functional cure could only be achieved (theoretically) reactivating those reservoirs.

Sorry for the questions
Thanks =) This stuff is pretty interesting to me.

His particular immune system manufactured those antibodies to fight his hiv infection. He was lucky. The question is why did his immune system manufacture those antibodies and how can we get our immune system to do the same. That is adaptive immunity.

A functional cure means the virus isn't eradicated from your body, but your immune system can keep it in check. Sort of like shingles when you have a strong immune system.

Here's a definition:"ADAPTIVE IMMUNITY Also known as acquired immunity, it describes the response of antigen-specific lymphocytes to antigen and the development of immunological memory. It is mediated by the clonal selection of lymphocytes"

Here's a full explanation:

Adaptive Immunity Explained


CD8+ T lymphocytes and cytotoxicity
Main article: Cytotoxic T cell
Cytotoxic T cells (also known as TC, killer T cell, or cytotoxic T-lymphocyte (CTL)) are a sub-group of T cells which induce the death of cells that are infected with viruses (and other pathogens), or are otherwise damaged or dysfunctional.[1]

 

Killer T cells—also called cytotoxic T lymphocytes or CTL-directly attack other cells carrying certain foreign or abnormal molecules on their surfaces[5].Naive cytotoxic T cells are activated when their T-cell receptor (TCR) strongly interacts with a peptide-bound MHC class I molecule. This affinity depends on the type and orientation of the antigen/MHC complex, and is what keeps the CTL and infected cell bound together.[1] Once activated, the CTL undergoes a process called clonal expansion in which it gains functionality, and divides rapidly, to produce an army of “armed”-effector cells. Activated CTL will then travel throughout the body in search of cells bearing that unique MHC Class I + peptide.

When exposed to these infected or dysfunctional somatic cells, effector CTL release perforin and granulysin: cytotoxins which form pores in the target cell's plasma membrane, allowing ions and water to flow into the infected cell, and causing it to burst or lyse.[1] CTL release granzyme, a serine protease that enters cells via pores to induce apoptosis (cell death). To limit extensive tissue damage during an infection, CTL activation is tightly controlled and generally requires a very strong MHC/antigen activation signal, or additional activation signals provided by "helper" T-cells (see below).[1]

Upon resolution of the infection, most of the effector cells will die and be cleared away by phagocytes, but a few of these cells will be retained as memory cells.[3] Upon a later encounter with the same antigen, these memory cells quickly differentiate into effector cells, dramatically shortening the time required to mount an effective response.





















v




Offline dingowarrior

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Re: Two naturally occurring antibodies discovered
« Reply #11 on: July 10, 2010, 11:55:13 AM »
At the risk of sounded not very bright, can someone explain in "laymen" terms what this means and if its indeed a substantial step forward towards a cure and or vaccine?

DingoWarrior

Offline Inchlingblue

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Re: Two naturally occurring antibodies discovered
« Reply #12 on: July 10, 2010, 12:02:04 PM »
At the risk of sounded not very bright, can someone explain in "laymen" terms what this means and if its indeed a substantial step forward towards a cure and or vaccine?

DingoWarrior

I thought this article from WSJ did a good job of explaining it all:

http://online.wsj.com/article/SB10001424052748703609004575355072271264394.html

Offline tennisplayer56

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Re: Two naturally occurring antibodies discovered
« Reply #13 on: July 10, 2010, 12:20:53 PM »

A functional cure means the virus isn't eradicated from your body, but your immune system can keep it in check. Sort of like shingles when you have a strong immune system.


So does that mean those that are elite-controllers are considered functionally cured? Since they dont require meds or anything but the virus is under control.

Offline dingowarrior

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Re: Two naturally occurring antibodies discovered
« Reply #14 on: July 10, 2010, 01:15:22 PM »
I thought this article from WSJ did a good job of explaining it all:

http://online.wsj.com/article/SB10001424052748703609004575355072271264394.html

Thank you, that helped clear things up ..Now, the only thing,what about those of us who are already infected??
Dont get me wrong, a breakthru like this is great..A huge step,but I hope this will somehow also help those living with the virus.

Offline Inchlingblue

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Re: Two naturally occurring antibodies discovered
« Reply #15 on: July 10, 2010, 01:18:22 PM »
Thank you, that helped clear things up ..Now, the only thing,what about those of us who are already infected??
Dont get me wrong, a breakthru like this is great..A huge step,but I hope this will somehow also help those living with the virus.

I personally think it's too early to know for sure.

I have more faith in gene therapy, not only used in the way that has been reported recently in which stem cells are programmed to be HIV-resistant but also when it comes to programming genes to produce endless supplies of antibodies, something Nobel laureate David Baltimore is working on.
« Last Edit: July 10, 2010, 01:29:47 PM by Inchlingblue »

Offline dingowarrior

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Re: Two naturally occurring antibodies discovered
« Reply #16 on: July 10, 2010, 01:28:56 PM »
I personally think it's too early to know for sure.

I have more faith in gene therapy, not only used in the way that has been reported recently in which stem cells are programmed to be HIV-resistant but even when it comes to programming genes to produce antibodies, something David Baltimore is working on.
I personally think it's too early to know for sure.

I have more faith in gene therapy, not only used in the way that has been reported recently in which stem cells are programmed to be HIV-resistant but even when it comes to programming genes to produce antibodies, something David Baltimore is working on.

I think you and I are on the same page, my sentiments exactly.

Offline veritas

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Re: Two naturally occurring antibodies discovered
« Reply #17 on: July 11, 2010, 05:26:24 AM »
So does that mean those that are elite-controllers are considered functionally cured? Since they dont require meds or anything but the virus is under control.

Not necessarily. Read this pdf by David Evans, the science has progressed since this article:

http://www.hihaf.org/newsletterfiles/08-10.pdf

If the virus starts to progress in an elite controller (as has happened to some on these forums), they did not have a functional cure. Also, some elite controllers experience side effects due to a continuous yet controlled viral load.


v

Offline veritas

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Re: Two naturally occurring antibodies discovered
« Reply #18 on: July 11, 2010, 05:44:13 AM »

Interesting Time Article ("if you don't have good antibodies, you don't have a vaccine"):

http://www.time.com/time/health/article/0,8599,2002992,00.html


v

Offline dingowarrior

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Re: Two naturally occurring antibodies discovered
« Reply #19 on: July 11, 2010, 12:06:17 PM »
Interesting Time Article ("if you don't have good antibodies, you don't have a vaccine"):

http://www.time.com/time/health/article/0,8599,2002992,00.html


v

Yes, but still sounds hopeful and promising.

Offline veritas

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Re: Two naturally occurring antibodies discovered
« Reply #20 on: July 11, 2010, 12:42:02 PM »

dingo,

No arguement with the find being hopeful and promising  --- it gives them the pathway to a vaccine.


v

Offline dingowarrior

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Re: Two naturally occurring antibodies discovered
« Reply #21 on: July 11, 2010, 03:09:59 PM »
dingo,

No arguement with the find being hopeful and promising  --- it gives them the pathway to a vaccine.



v

Indeed :)

Offline Boze

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Re: Two naturally occurring antibodies discovered
« Reply #22 on: July 11, 2010, 03:17:49 PM »
Does anybody see the similarity between Donor 45 and http://en.wikipedia.org/wiki/Henrietta_Lacks

==========
Aug08 - Seroconversion
Mar10 - Diagnosis; cd4 690 - VL 19,000
Apr10 - cd4 600
May10 - VL 4,500
Jun10 - started Atripla ; VL 113
Jul 10 - UD vl, CD4 590
Aug 10 - UD, CD4 810, 52%
Nov 10 - UD, CD4 980

Offline OneTampa

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Re: Two naturally occurring antibodies discovered
« Reply #23 on: July 11, 2010, 04:56:25 PM »
CNN also conducted an interview with two activists:

http://www.youtube.com/watch?v=dCS76SpjDvA

"He is my oldest child. The shy and retiring one over there with the Haitian headdress serving pescaíto frito."

Offline Ravhyn

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Re: Two naturally occurring antibodies discovered
« Reply #24 on: July 12, 2010, 09:29:32 AM »
I think like many of you it will take time to see where this is going although it does sound promising.

and like many of you, I'm still running with the gene therapy (lol)  but I see a lot coming our way over the next couple of years as scientist start breaking down more and learning how we all tick with the virus in us. 

IMHO, and no one jump me over this please, I think in another decade we can see all these things coming together and wether or not its a cure, vaccine, or something. I think within a decade maybe two at the most will be stepping away from HAART for good. 
April 2006 - Sero-Conversion
December 2009 - Diagnosed
Jan 2010- VL 3,800 CD4 152
Summer 2010 VL UD, CD4 over 200
September 2010 VL UD, CD4 324
March 2011 VL UD, CD4 477
May 2011 VL UD, 338

Offline ElZorro

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Re: Two naturally occurring antibodies discovered
« Reply #25 on: July 12, 2010, 10:14:57 PM »
5 years, Ravhyn...that's where my money is. There's gonna be a huge change in the next five years  ;)

Offline Miss Philicia

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Re: Two naturally occurring antibodies discovered
« Reply #26 on: July 12, 2010, 10:56:58 PM »
I heard that one a decade ago.
"I’ve slept with enough men to know that I’m not gay"

Online tednlou2

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Re: Two naturally occurring antibodies discovered
« Reply #27 on: July 13, 2010, 01:24:35 AM »
Why the different figures in the media?  I first heard 2 antibodies.  Then heard 3 were actually found.  I heard it would cover 90% of strains, then heard 91%, and just heard 99% in the interview on CNN below.

About what someone said here about functionally cured meaning you still have the virus but your immune system keeps it in check--  The german man was said to be functionally cured and they can't find the virus in his body, right?  Isn't that different that your body being able to keep HIV in check? 

Below is the link to a CNN interview with anchor Don Lemon.  They actually get a little ahead of themselves by talking about whether the vaccine should be mandatory.  However, I guess it is good to start discussing these things now.

http://www.thebody.com/content/art57389.html

Offline veritas

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Re: Two naturally occurring antibodies discovered
« Reply #28 on: July 13, 2010, 05:34:51 AM »

Tednlou2,

A functional cure means "a lifetime with no disease progression, no symtoms, and no prolonged ARV treatment. " They are being careful with the Berlin patient. A CURE would mean the complete eradication of the virus from the body (all reservoirs etc.). Hard to prove.

I'm not surprised the percentages are all over the place with respect to strains in the media. Damn the facts get the story out. I'll stick with the 90% ---- thats a great number.

CNN is way ahead of themselves. It should boil down to individual choice.

v

Offline ElZorro

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Re: Two naturally occurring antibodies discovered
« Reply #29 on: July 13, 2010, 11:03:08 AM »
The CNN interview seemed to only address a preventative vaccine. Will this find be applicable to therapeutic treatment?

Offline tennisplayer56

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Re: Two naturally occurring antibodies discovered
« Reply #30 on: July 13, 2010, 11:20:19 AM »
So a functional cure means that the virus is still transmittable right?

Offline Inchlingblue

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Re: Two naturally occurring antibodies discovered
« Reply #31 on: July 13, 2010, 11:23:58 AM »
Why the different figures in the media?  I first heard 2 antibodies.  Then heard 3 were actually found.  I heard it would cover 90% of strains, then heard 91%, and just heard 99% in the interview on CNN below.

About what someone said here about functionally cured meaning you still have the virus but your immune system keeps it in check--  The german man was said to be functionally cured and they can't find the virus in his body, right?  Isn't that different that your body being able to keep HIV in check?  
 

There are two types of cures: functional and sterilizing. Functional cure means that there is still virus in your body but  you are able to live with the virus without the virus causing any (or much) harm and without having to take meds every day. This could potentially be achieved any number of ways such as with gene therapy. If the immune system can be re-jigged with new HIV-resistant cells, HIV would still be present but it would not be able to enter any cells and replicate so that would be considered a functional cure.

A sterilizing cure means that all the HIV is cleared from the body. Right now, HAART does a great job of removing actively replicating HIV but cannot reach the HIV lying dormant in the reservoirs. If a way was found to clear the reservoirs this would be considered a sterilizing cure.

As far as these new antibodies go, VRC01 and VRC02 neutralized 91 percent of HIV strains, and VRC03, neutralized 57 percent. A lot of the news reports focused on just two of them, VRC01 and VRC02, since they were so much more powerful than VRC03, which got short shrift. The guy in the CNN interview said 99%, I assume he is mistaken by that number. There were other recent antibodies found in September 2009, which I linked in an earlier post here. It's possible that he means 99% if you were to combine all the various broadly neutralizing antibodies together.

The CNN interview seemed to only address a preventative vaccine. Will this find be applicable to therapeutic treatment?

The challenge here, whether a person is HIV positive or negative is to get everyone's bodies to start producing these antibodies. In the case of a preventive vaccine the challenge is to get a sustained and strong immune response not requiring constant boosters. In the case of someone who already has HIV, the immune system may be too damaged to produce them. And even if they are produced it's too soon to know how effective they can be once HIV has already taken hold. It's too early to know in either case.

David Baltimore, a Nobel laureate and respected HIV researcher, is working on re-programming genes so that they produce an endless supply of antibodies. This would bypass the problem of trying to get the immune system to do it. And it would also potentially allow for a good mix of various broadly neutralizing antibodies, kind of like a "cocktail," which would likely work better than just one or even two of them.

The important thing about the discovery of these broadly neutralizing antibodies, the ones recently found and those found in September 2009, is that until recently there was doubt whether they even existed, whether the body was capable of making them at all.

There are now newer and more effective methods for finding antibodies; others have been found that are not even in the news. More will likely be found in the near future.

I'd love to know more details about the HIV progression or lack thereof with the people who naturally produce these antibodies. It's believed they were not protected from HIV to begin with because their bodies did not begin to make the antibodies until after they already had HIV, iow not quick enough to be able to halt the infection. Donor 45 is not an elite controller so I wonder what kind of advantage the antibody has given him.
« Last Edit: July 13, 2010, 02:16:17 PM by Inchlingblue »

Offline tennisplayer56

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Re: Two naturally occurring antibodies discovered
« Reply #32 on: July 13, 2010, 01:58:46 PM »
There are two types of cures: functional and sterilizing. Functional cure means that there is still virus in your body but  you are able to live with the virus without the virus causing any (or much) harm and without having to take meds every day. This could potentially be achieved any number of ways such as with gene therapy. If the immune system can be re-jigged with new HIV-resistant cells, HIV would still be present but it would not be able to enter any cells and replicate so that would be considered a functional cure.

A sterilizing cure means that all the HIV is cleared from the body. Right now, HAART does a great job of removing actively replicating HIV but cannot reach the HIV lying dormant in the reservoirs. If a way was found to clear the reservoirs this would be considered a sterilizing cure.

As far as these new antibodies go, VRC01 and VRC02 neutralized 91 percent of HIV strains, and VRC03, neutralized 57 percent. A lot of the news reports focused on just two of them, VRC01 and VRC02, since they were so much more powerful than VRC03, which got short shrift. The guy in the CNN interview said 99%, I assume he is mistaken by that number. There were other recent antibodies found in September 2009, which I linked in an earlier post here. It's possible that he means 99% if you were to combine all the various broadly neutralizing antibodies together.

The challenge here, whether a person is HIV positive or negative is to get everyone's bodies to start producing these antibodies. In the case of a preventive vaccine the challenge is to get a sustained and strong immune response not requiring constant boosters. In the case of someone who already has HIV, the immune system may be too damaged to produce them. And even if they are produced it's too soon to know how effective they can be once HIV has already taken hold. It's too early to know in either case..

David Baltimore, a Nobel laureate and respected HIV researcher, is working on re-programming genes so that they produce an endless supply of antibodies. This would bypass the problem of trying to get the immune system to do it. And it would also potentially allow for a good mix of various broadly neutralizing antibodies, kind of like a "cocktail," which would likely work better than just one or even two of them.

The important thing about the discovery of these broadly neutralizing antibodies, the ones recently found and those found in September 2009, is that until recently there was doubt whether they even existed, whether the body was capable of making them at all.

There are now newer and more effective methods for finding antibodies; others have been found that are not even in the news. More will likely be found in the near future.

I'd love to know more details about the HIV progression or lack thereof with the people who naturally produce these antibodies. It's believed they were not protected from HIV to begin with because their bodies did not begin to make the antibodies until after they already had HIV, iow not quick enough to be able to halt the infection. Donor 45 is not an elite controller so I wonder what kind of advantage the antibody has given him.


Hi Ichlingblue

I dont want to belabor this point too much, but i was hoping you could clarify something for me. You didn't quite answer my previous answer, which was that if you theroetically had a functional cure, would the virus still be transmittable? Im just curious because from what you said, it seems that elite-controllers are th definition of functionally cured: they live with the virus, don't require meds, and they're cells contain a mutation that renders HIV from entering the cells. At least to some degree anyways. But the virus is still transmittable.

Also in terms of these VRCO broadly neutralizing antibodies is that they are produing a functional cure? If the body is able to produce them, then theoretically there would be no neeed for meds and the virus would be checked...but the latent reseroirs would still be present. It seems that broadly neutralizing antibodies only have the of eliminating the inconvenience of drugs? But can it do more than what modern HAART can do? Or is it too early to tell and i'm just talking IF's. hahahaha...

thanks!!

Offline veritas

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Re: Two naturally occurring antibodies discovered
« Reply #33 on: July 13, 2010, 04:55:05 PM »

tennisplayer56,

I admire your inquisitiveness. I wish we had the answers to all your questions. However, we don't. They just discovered these antibodies and as far as we know they are only helping Donor 45 at present. We're dealing with theoreticals and potentials. Too early to tell!

v

ps: Why do you want to know if you will still transmit the virus? ;)

Offline Inchlingblue

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Re: Two naturally occurring antibodies discovered
« Reply #34 on: July 13, 2010, 06:46:20 PM »

Hi Ichlingblue

I dont want to belabor this point too much, but i was hoping you could clarify something for me. You didn't quite answer my previous answer, which was that if you theroetically had a functional cure, would the virus still be transmittable? Im just curious because from what you said, it seems that elite-controllers are th definition of functionally cured: they live with the virus, don't require meds, and they're cells contain a mutation that renders HIV from entering the cells. At least to some degree anyways. But the virus is still transmittable.

Also in terms of these VRCO broadly neutralizing antibodies is that they are produing a functional cure? If the body is able to produce them, then theoretically there would be no neeed for meds and the virus would be checked...but the latent reseroirs would still be present. It seems that broadly neutralizing antibodies only have the of eliminating the inconvenience of drugs? But can it do more than what modern HAART can do? Or is it too early to tell and i'm just talking IF's. hahahaha...

thanks!!

It's true that a functional cure can be seen as being similar to what happens with an elite controller, i.e. the body is able to control HIV without meds. By the way, as an aside, you mention that elite controllers  "contain a mutation that renders HIV from entering the cells." There have been many studies of ECs and lots of information is known regarding how they can control HIV but it's not because their cells have the delta 32 mutation and lack CCR5. People with that mutation are virtually immune to HIV, which is different from an elite controller.

As veritas says, it's too soon to know whether these antibodies will be able to incur a functional cure or not and it's also too soon to know if a person who is functionally cured would be able to transmit the virus or not.


Offline tennisplayer56

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Re: Two naturally occurring antibodies discovered
« Reply #35 on: July 13, 2010, 08:22:38 PM »
tennisplayer56,

I admire your inquisitiveness. I wish we had the answers to all your questions. However, we don't. They just discovered these antibodies and as far as we know they are only helping Donor 45 at present. We're dealing with theoreticals and potentials. Too early to tell!

v

ps: Why do you want to know if you will still transmit the virus? ;)

Well, you write as if to ask if I peronsally want to still transmit the viurus. haha.

The real reason is that after reading the national HIV/AIDS strategy, i thought that decreasing transmission of the virus seems like the governmental plan of action. But that plan looks to be more focused in prevention than anything else. A method that would make stop transmission in current HIV+ people seems to have the same effect as all the preventative programs in place out there.
Plus, with current advances in medicine, the other than the inconvenience of popping pills everyday, HAART has the potential to be side effect free.
Plus if you think about it, if some treatment has the ability to stop the transmission of the virus but you still have it in your body, the stigma of HIV will start to disappear. It can, in many ways, cease to be a STI.
I dunno, all this talk about functional vs absolute eradication just got me thinking about stuff.

Back to work. TTYL

Offline Ravhyn

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Re: Two naturally occurring antibodies discovered
« Reply #36 on: July 17, 2010, 11:54:15 PM »
On the news of the news not getting it (yea...I'm a little drunk bare with me here)

I went to a barbeque tonight where my mom was like "I heard theres been a cure found"

this progressed into a conversation where I learned several people misunderstood the news (Fox, CNN whatever it was) and came to work to inform my mom a cure had been found.

-_-  I really hate the news...

April 2006 - Sero-Conversion
December 2009 - Diagnosed
Jan 2010- VL 3,800 CD4 152
Summer 2010 VL UD, CD4 over 200
September 2010 VL UD, CD4 324
March 2011 VL UD, CD4 477
May 2011 VL UD, 338

 


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