Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists shed new light on how antibodies fight HIV

10.09.2007
New findings may further efforts to create AIDS vaccine

By furthering scientists’ understanding of the molecular mechanisms that separate the minority of successful HIV antibodies from the majority of ineffective antibodies, the work may have implications for future attempts to design an HIV vaccine.

The study was published on September 6, 2007, in the journal Nature.

“This study is part of the effort to understand how protection against HIV occurs,” says Dennis Burton, a professor at The Scripps Research Institute. “If we really understand this, then we can design tailor-made vaccines in a way that has never been done before.”

... more about:
»B12 »CASCADE »HIV »LALA »Pathogen »Vaccine »immune cell »infected »receptor

Although vaccines have long been used with great success to prevent diseases, scientists are still learning about the exact mechanisms of how vaccines work and how the antibodies that vaccines prompt the body to create can neutralize a pathogen. The spread of HIV, which is resistant to most antibodies the body produces against it, has made fully understanding this method of action more urgent.

With this in mind, Burton and colleagues sought to tease apart the action of the b12 antibody-one of the rare antibodies that protects against the HIV virus. The antibody, first identified by Burton, Scripps Research Professor Carlos Barbas III, and colleagues in 1992, originally came from the bone marrow of a 31-year-old male who had been HIV positive without symptoms for six years.

In the current study, researchers created mutated versions of b12 to see what effect various changes would have on the antibody’s effectiveness.

“Hopefully, we can work backwards towards a vaccine, using b12 and the very few other really great, broadly neutralizing antibodies against HIV that have been found,” says Scripps Research Senior Research Associate Ann Hessell, who was first author of the Nature paper jointly with Lars Hangartner, a Scripps Research postdoctoral fellow.

Results from the new study suggest the importance of antibody activity against both infected cells and free virus for effective protection. As well as simply binding to HIV, protection was dependent upon the ability of antibodies to interact with immune cell Fc receptors.

Fc receptors are found on the surface of immune cells, such as natural killer cells. The Fc receptor binds to the Fc region of an antibody after an antibody binds to a pathogen, targeting the pathogen for attack by the immune system. Although Fc receptor function was known to be important for the function of antibodies against other diseases, a role in protecting against HIV had never before been demonstrated.

Burton’s team examined the ability of two antibodies mutated from b12, dubbed KA and LALA, to prevent infection using the SHIV/macaque model, in which macaques are challenged with a hybrid human-simian virus that infects the model but is recognized by human antibodies. The KA antibody contained a mutation that prevented it from interacting with the complement cascade, a major component of the immune system responsible for destroying invading pathogens. The LALA antibody contained a mutation that rendered it unable to interact with either the complement pathway or the Fc receptor.

In both mutants, the site where the antibody binds to free-floating virus was unaltered, allowing the researchers specifically to investigate the importance of the complement cascade and Fc receptor system for preventing infection.

“We saw that the KA antibody, which could still bind to the Fc receptors on the immune cells but not to the complement cascade, protected the animals from becoming infected just as the wild type b12 antibody,” says Hessell. “In contrast, the LALA group became infected much like the controls.”

The results provide the first evidence that the Fc receptor, but not the complement cascade, is important to the function of the b12 antibody in preventing HIV infection.

Additional in vitro experiments revealed that the wild type and KA antibodies, but not the LALA antibody, blocked infection more efficiently in the presence of other effector cells of the immune system.

“Our results are fully consistent with the antibody doing two jobs,” says Burton, “job one, stick to the virus; job two, recruit immune cells to come and kill infected cells.”

Keith McKeown | EurekAlert!
Further information:
http://www.scripps.edu

Further reports about: B12 CASCADE HIV LALA Pathogen Vaccine immune cell infected receptor

More articles from Life Sciences:

nachricht NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation

nachricht Pollen taxi for bacteria
18.07.2018 | Technische Universität München

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

NYSCF researchers develop novel bioengineering technique for personalized bone grafts

18.07.2018 | Life Sciences

Machine-learning predicted a superhard and high-energy-density tungsten nitride

18.07.2018 | Materials Sciences

Why might reading make myopic?

18.07.2018 | Health and Medicine

VideoLinks
Science & Research
Overview of more VideoLinks >>>