Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Body’s own antibodies may drive new strains of HIV

18.03.2003


Study Sheds light on HIV mutation process; May help guide AIDS vaccine development

Scientists in California have provided the first detailed look at how human antibodies, proteins critical for the body’s defense against invading pathogens, may actually drive human immunodeficiency virus (HIV) to mutate and escape detection by the immune system. The findings, reported online March 18 in the Proceedings of the National Academy of Sciences, may be key in efforts to develop an effective AIDS vaccine.

A team led by Douglas D. Richman, MD, a virologist and physician with the Veterans Affairs (VA) San Diego Healthcare System and the University of California, San Diego (UCSD) School of Medicine, found that patients infected with HIV rapidly develop a strong antibody response against the virus. But the same antibodies tasked with recognizing and disabling the germ appear to force its ongoing evolution into new strains that dance around the antibody response and continue to replicate.



"The neutralizing antibodies are exerting a very strong selective pressure on the virus, and the virus is continually mutating to avoid it," said Richman, a noted AIDS researcher who recently won VA’s Middleton Award, the agency’s highest honor for biomedical researchers.

The researchers used sophisticated new technology, made by California-based ViroLogic, Inc., to clone actual virus from the blood plasma of HIV patients and genetically combine it with a gene that makes luciferase, the same light-emitting enzyme in fireflies. The glowing enzyme helped the scientists track the virus’ replication.

Richman and colleagues took viral samples periodically from HIV patients and incubated the virus with antibody-containing plasma samples from the same patients. Blood plasma contains antibodies but no white blood cells. This way, the researchers could tease out the effects of antibodies alone on the virus, independent of the rest of the immune system.

The results, based on tests of 19 patients over 39 months, showed that most patients developed a high concentration, or titer, of antibodies to HIV within a few months, and the antibodies continually changed their "spectrum of activity" to keep pace with the ever-changing virus. That is, the antibodies evolved in their ability to recognize different protein shapes on the outer coating of the virus.

However the virus consistently evolved faster than the antibody response, developing new protein structures on its surface, so that antibodies from previous months’ samples were ineffective in neutralizing new virus from the same patient.

"The bad news is that the virus is always staying a step ahead, and the neutralizing antibody response can’t control it," said Richman.

At the same time, Richman said neutralizing antibodies could hold promise as a therapy, or vaccine, if scientists can engineer them to recognize many different strains of virus.

"An optimistic view is that this antibody response is a very potent selective force," said Richman. "If it were present at the time of exposure [to the virus], it could provide some protection."

The AIDS virus has been described as a "genetic moving target" because of its frustrating ability to rapidly mutate and escape the body’s efforts to neutralize or destroy it. In fact, up to dozens of strains can develop within the same person. Also, HIV infects and disables the very immune cells, helper T cells, which are supposed to mobilize the immune system against the virus. Richman’s study is the first to track in detail how the virus outpaces the antibody response over time.

Since 1987, researchers have studied about 60 potential HIV vaccines to help stem the AIDS epidemic. So far, no vaccine has won Food and Drug Administration approval as safe and effective. Most scientists agree that for a vaccine to work, it will need to activate both arms of the immune system: antibodies, which are key in thwarting the initial infection; and killer white blood cells, which provide longer-term protection. In recent years, AIDS scientists have made progress on the cellular front; several vaccines using this approach are in the pipeline for clinical trials. But understanding how to get neutralizing antibodies to work against HIV has proved a tougher challenge.

According to the Centers for Disease Control and Prevention, 800,000 to 900,000 Americans are living with HIV infection. VA, the nation’s largest health-care system, is also the nation’s largest single provider of health care to those with HIV. In fiscal year 2001, more than 18,500 veterans received care for HIV at VA medical centers and clinics.


###
Richman directs VA’s Research Center for AIDS and HIV Infection and the Center for AIDS Research at UCSD. Collaborating with him on the study were Susan J. Little, MD, a principal investigator in UCSD’s Antiviral Research Center and a VA infectious disease specialist; and Terri L. Wrin and Christos J. Petropoulos of ViroLogic, Inc. The firm, which specializes in HIV drug resistance testing, developed the DNA viral test used in the study. Richman serves on the company’s scientific advisory board.

Funding for the study was provided by the National Institutes of Health, VA, and UCSD.

Cynthia Butler (VA)
(858) 552-4373
Cynthia.butler@med.va.gov

Sue Pondrom (UCSD)
(619) 543-6163
Spondrom@ucsd.edu

Cynthia Butler | EurekAlert!

More articles from Health and Medicine:

nachricht How cancer metastasis happens: Researchers reveal a key mechanism
19.01.2018 | Weill Cornell Medicine

nachricht Researchers identify new way to unmask melanoma cells to the immune system
17.01.2018 | Duke University Medical Center

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Thanks for the memory: NIST takes a deep look at memristors

22.01.2018 | Materials Sciences

Radioactivity from oil and gas wastewater persists in Pennsylvania stream sediments

22.01.2018 | Earth Sciences

Saarland University bioinformaticians compute gene sequences inherited from each parent

22.01.2018 | Life Sciences

VideoLinks Wissenschaft & Forschung
Overview of more VideoLinks >>>