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Antibody that Neutralizes Most HIV Strains Described by Scientists
A group of scientists from The Scripps Research Institute and several other institutions has solved the structure of a rare human antibody that broadly neutralizes human immunodeficiency virus (HIV), which causes acquired immunodeficiency syndrome (AIDS).
Antibody that Neutralizes Most HIV Strains Described by Scientists at The Scripps Research Institute
La Jolla, CA. February 22, 2005—A group of scientists from The Scripps Research Institute and several other institutions has solved the structure of a rare human antibody that broadly neutralizes human immunodeficiency virus (HIV), which causes acquired immunodeficiency syndrome (AIDS).
Neutralizing antibodies are soluble proteins that are secreted by adaptive immune cells into the bloodstream, following exposure to a virus. In the bloodstream, antibodies bind to viral particles in circulation, prevent them from infecting human cells, and lead to the viral particles’ destruction—thus neutralizing them.
Because neutralizing antibodies attack the virus before it enters cells, they can prevent HIV infection if they are present prior to exposure to the virus. An HIV vaccine would seek to elicit these neutralizing antibodies—just as existing vaccines against diseases such as measles, polio, hepatitis B, and hepatitis A elicit neutralizing antibodies against those viruses.
However, this is easier said than done. The body makes many antibodies against HIV, but they are almost always unable to neutralize the virus. Nonetheless, the immune systems of some patients with HIV have beaten the odds and have produced effective neutralizing antibodies. The structure of one of these, called 4E10, is described in the latest issue of the journal Immunity.
“This antibody is very broadly active,” says Scripps Research Professor Dennis Burton, Ph.D., who led the research with Scripps Research Professor Ian Wilson, D.Phil. “It neutralized nearly 100 different viral strains of HIV from all over the world. [During tests in the laboratory], every one of them was neutralized.”
4E10 was isolated from an HIV-positive individual about a decade ago by Burton and Wilson’s collaborator Hermann Katinger, a doctor at the Institute for Applied Microbiology of the University of Agriculture in Vienna, Austria, and one of the authors of the paper.
Significantly, the structure shows what an effective HIV-neutralizing antibody can look like. 4E10 targets an area on the HIV surface protein GP41 that the virus uses to fuse its membrane to the membrane of a human cell it is infecting. The target area is unusually close to the virus’s membrane surface, and the antibody has an unusual adaptation that might help it stick to the virus close to the membrane—a “finger” of amino acids with a propensity to dip down into the membrane and bring the antibody in contact with the target area.
Moreover, since the structure shows what the “epitope” looks like—the area on the HIV surface to which 4E10 binds—this work gives scientists insight into how to reverse-engineer a component of an HIV vaccine. The structure of this antibody could be used as a template to design an epitope mimic that would stimulate the human immune system to make 4E10 or similar broadly neutralizing antibodies against HIV.
“Once one knows what the epitope is, one can design mimics of it much more easily,” says Wilson, who is an investigator in The Skaggs Institute for Chemical Biology at The Scripps Research Institute.
The research article, "Broadly Neutralizing Anti-HIV Antibody 4E10 Recognizes a Helical Conformation of a Highly Conserved Fusion-Associated Motif in gp41: Implications for Vaccine Design” is authored by Rosa M. F. Cardoso, Michael B. Zwick, Robyn L. Stanfield, Renate Kunert, James M. Binley, Hermann Katinger, Dennis R. Burton, and Ian A. Wilson, and appears in the February, 2005 issue of the journal Immunity. The article can be accessed by journal subscribers at: http://immunity.com.
The research was supported by the National Institute of General Medical Sciences (NIGMS), the National Institute of Allergy and Infectious Diseases (NIAID), the International AIDS Vaccine Initiative (IAVI), The Skaggs Institute for Research, an American Foundation for AIDS Research fellowship, and the Elizabeth Glaser Pediatric AIDS Foundation. Drs. Burton and Wilson are members of IAVI’s Neutralizing Antibody Consortium, a consortium of scientists working together to design vaccines to elicit broadly neutralizing antibodies to HIV-1.
About The Scripps Research Institute
The Scripps Research Institute in La Jolla, California and Palm Beach County, Florida, is one of the world's largest, private, non-profit biomedical research organizations. It stands at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its research into immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune diseases, cardiovascular diseases and synthetic vaccine development.
For more information contact:
Keith McKeown
10550 North Torrey Pines Road
La Jolla, California 92037
Tel: 858.784.8134
Fax: 858.784.8118
kmckeown [at] scripps.edu
La Jolla, CA. February 22, 2005—A group of scientists from The Scripps Research Institute and several other institutions has solved the structure of a rare human antibody that broadly neutralizes human immunodeficiency virus (HIV), which causes acquired immunodeficiency syndrome (AIDS).
Neutralizing antibodies are soluble proteins that are secreted by adaptive immune cells into the bloodstream, following exposure to a virus. In the bloodstream, antibodies bind to viral particles in circulation, prevent them from infecting human cells, and lead to the viral particles’ destruction—thus neutralizing them.
Because neutralizing antibodies attack the virus before it enters cells, they can prevent HIV infection if they are present prior to exposure to the virus. An HIV vaccine would seek to elicit these neutralizing antibodies—just as existing vaccines against diseases such as measles, polio, hepatitis B, and hepatitis A elicit neutralizing antibodies against those viruses.
However, this is easier said than done. The body makes many antibodies against HIV, but they are almost always unable to neutralize the virus. Nonetheless, the immune systems of some patients with HIV have beaten the odds and have produced effective neutralizing antibodies. The structure of one of these, called 4E10, is described in the latest issue of the journal Immunity.
“This antibody is very broadly active,” says Scripps Research Professor Dennis Burton, Ph.D., who led the research with Scripps Research Professor Ian Wilson, D.Phil. “It neutralized nearly 100 different viral strains of HIV from all over the world. [During tests in the laboratory], every one of them was neutralized.”
4E10 was isolated from an HIV-positive individual about a decade ago by Burton and Wilson’s collaborator Hermann Katinger, a doctor at the Institute for Applied Microbiology of the University of Agriculture in Vienna, Austria, and one of the authors of the paper.
Significantly, the structure shows what an effective HIV-neutralizing antibody can look like. 4E10 targets an area on the HIV surface protein GP41 that the virus uses to fuse its membrane to the membrane of a human cell it is infecting. The target area is unusually close to the virus’s membrane surface, and the antibody has an unusual adaptation that might help it stick to the virus close to the membrane—a “finger” of amino acids with a propensity to dip down into the membrane and bring the antibody in contact with the target area.
Moreover, since the structure shows what the “epitope” looks like—the area on the HIV surface to which 4E10 binds—this work gives scientists insight into how to reverse-engineer a component of an HIV vaccine. The structure of this antibody could be used as a template to design an epitope mimic that would stimulate the human immune system to make 4E10 or similar broadly neutralizing antibodies against HIV.
“Once one knows what the epitope is, one can design mimics of it much more easily,” says Wilson, who is an investigator in The Skaggs Institute for Chemical Biology at The Scripps Research Institute.
The research article, "Broadly Neutralizing Anti-HIV Antibody 4E10 Recognizes a Helical Conformation of a Highly Conserved Fusion-Associated Motif in gp41: Implications for Vaccine Design” is authored by Rosa M. F. Cardoso, Michael B. Zwick, Robyn L. Stanfield, Renate Kunert, James M. Binley, Hermann Katinger, Dennis R. Burton, and Ian A. Wilson, and appears in the February, 2005 issue of the journal Immunity. The article can be accessed by journal subscribers at: http://immunity.com.
The research was supported by the National Institute of General Medical Sciences (NIGMS), the National Institute of Allergy and Infectious Diseases (NIAID), the International AIDS Vaccine Initiative (IAVI), The Skaggs Institute for Research, an American Foundation for AIDS Research fellowship, and the Elizabeth Glaser Pediatric AIDS Foundation. Drs. Burton and Wilson are members of IAVI’s Neutralizing Antibody Consortium, a consortium of scientists working together to design vaccines to elicit broadly neutralizing antibodies to HIV-1.
About The Scripps Research Institute
The Scripps Research Institute in La Jolla, California and Palm Beach County, Florida, is one of the world's largest, private, non-profit biomedical research organizations. It stands at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its research into immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune diseases, cardiovascular diseases and synthetic vaccine development.
For more information contact:
Keith McKeown
10550 North Torrey Pines Road
La Jolla, California 92037
Tel: 858.784.8134
Fax: 858.784.8118
kmckeown [at] scripps.edu
For more information:
http://healthorbit.ca/NewsDetail.asp?opt=1...
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The existence of such an antibody implies the exsitence of a gene to code this protein. If the percentage of presence of such a gene in some subpopul;ations is greater than a very tiny amount, it implies that HIV/AIDS is NOT a new virus but that at some time in the past has caused selection pressure for resistance in that sub-population.
That would not be terribly unusual. Certainly you are aware that some virus diseases like measles (human distemper) are only moderately dangerous* in some human populations but caused severe deadly epidemics when reaching populations without such resistance. Given modern transportation and mixing of populations, that could then cause a rise above the low levels of the disease in resistant populations. The mathematics of epidemics (whether a disease will propogate in the population and at what level of infection stability is or is not reached) is very complicated.
* -- Do NOT bother telling me that measles in a resistant popualtion is trivial. I grew up before there was a vaccine against measles. I was one of the lucky ones who not only survived measles encephalitis but apparently did not suffer much mental impairment.
That would not be terribly unusual. Certainly you are aware that some virus diseases like measles (human distemper) are only moderately dangerous* in some human populations but caused severe deadly epidemics when reaching populations without such resistance. Given modern transportation and mixing of populations, that could then cause a rise above the low levels of the disease in resistant populations. The mathematics of epidemics (whether a disease will propogate in the population and at what level of infection stability is or is not reached) is very complicated.
* -- Do NOT bother telling me that measles in a resistant popualtion is trivial. I grew up before there was a vaccine against measles. I was one of the lucky ones who not only survived measles encephalitis but apparently did not suffer much mental impairment.
Well... it's been demonstrated by researchers at UC Berkeley and elsewhere that the frequency of a cell receptor (I forgot the name, but I'm sure you could find it easily) which provides immunity to individuals possessing a rare gene occurs at a far higher frequency in eastern europe than you would expect if it hadn't increased very rapidly by providing positive selection to people surviving an epidemic since about 1200. The highest concentration of this receptor is around Latvia to Hungary where about 8% might have it, and it might have had something to do with smallpox.
The deaths from so-called AIDS are a combo of causes, from poverty, malnutrition to immune suppressing drugs like methamphetamine. Several organizations are opposed to this info being regarded as true, so the HIV causes AIDS myth may prevail for some time..
We will continue to post info that the pharmaceutical corporations are profiting from the AIDS hoax..
After all, who would get rich if eating and living healthy was the only cure ever needed?
ACT-UP!! Queer Resistance to the AIDS hoax!!
We will continue to post info that the pharmaceutical corporations are profiting from the AIDS hoax..
After all, who would get rich if eating and living healthy was the only cure ever needed?
ACT-UP!! Queer Resistance to the AIDS hoax!!
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