Scientists create first successful libraries of avian flu virus antibodies

April 14, 2008

An international group of American and Turkish research scientists, led by Sea Lane Biotechnologies, has created the first comprehensive monoclonal antibody libraries against avian influenza (H5N1) using samples from survivors of the 2005/2006 "bird flu" outbreak in Turkey.

These antibody libraries hold the promise for developing a therapy that could stop a pandemic in its tracks and provide treatment to those infected, as well as potentially pointing the way towards the development of a universal flu vaccine. The expanded treatment and containment options offered by Sea Lane’s antibody libraries could help provide healthcare officials, researchers, and governments with unprecedented resources to combat this serious global health threat.

“Three global influenza pandemics have occurred within the past 100 years, each with devastating consequences,” said Richard A. Lerner, the Lita Annenberg Hazen Professor of Immunochemistry at, and President of, the Scripps Research Institute (La Jolla, CA) who collaborated with Sea Lane on the study. “Our study holds out the hope that a new outbreak could potentially be stopped at an early stage, and that effective treatment could be available to those infected.”

The study is being published in this week’s Early Edition of the journal Proceedings of the National Academy of Sciences.

So far, the new antibody libraries reported in the study have yielded more than 300 unique monoclonal antibodies that are active against H5N1 antigens—foreign substances that produce an immune system response. From this group, the authors identified several broadly neutralizing antibodies that were effective against a number of contemporary subtypes of H5 (avian) flu.

Moving Towards A Universal Influenza Vaccine

The new research reported here suggests that the antibodies recovered from the avian flu survivors may point to an exploitable weak spot in the virus, offering the tantalizing possibility that a “universal” vaccine against all strains might be made.

Remarkably, three of the more than 300 antibodies catalogued have been found to neutralize both the H1 (common seasonal flu) and H5 (avian) subtypes. “The antibodies we have isolated have the potential to be used directly as therapeutic agents against multiple influenza subtypes, permitting the resolution of infection upon administration to an infected individual,” said Peter Palese, the Horace W. Goldsmith Professor & Chairman of Microbiology at The Mount Sinai School of Medicine (New York, NY), another collaborator on the project.

“Perhaps most importantly, these antibodies may be used to identify cross-reactive epitopes on the hemagglutinin protein of an influenza virus. Identification of such epitopes may allow the rational design of vaccines with cross-subtype neutralizing activity. Such vaccines would constitute a major advance on current technology, and would be a first step towards the design of a universal influenza vaccine,” noted Palese.

Preventing The Worst-Case Scenario – Another Global Influenza Pandemic

Human infection with the avian flu virus H5N1 was first reported in 1997. Since 2003, according to the World Health Organization, more than 370 confirmed cases of human infection have been reported in 14 countries.

While overwhelmingly confined to bird populations in Asia and Europe, the H5N1 avian flu virus has shown its ability to infect humans and has killed more than 230 people around the world. Epidemiologists remain concerned that the virus will one day mutate and be able to spread more readily between people, sparking a global pandemic. The 1918-1920 Spanish flu, which shows evidence of originating in birds, killed somewhere between 40 and 100 million people.

The antibodies recovered from these H5N1 survivor libraries, described in the report, provide opportunities for passive immunization with monoclonal antibodies that could help future individuals infected with H5N1 successfully overcome infection. Monoclonal antibody therapy is known as passive immunotherapy because patients are treated with antibodies that were made outside of their own immune systems instead of those actively made internally.

The potential for passive immunization against influenza has been evident since the Spanish influenza pandemic nearly a century ago, where the benefits of transfused blood reduced the risk of mortality by more than 50 percent. Additionally, the benefits of treatment with convalescent plasma have begun to be reported in instances of H5N1, while passive immunization with human and mouse monoclonal antibodies have been shown to protect animals from death, even when given after H5N1 infection.

Offers Additional Therapeutic Potential

“The antibodies we recovered from Turkey have important and broad potential," said Michael Horowitz, Chief Operating Officer for Sea Lane. "They could lead the way to providing significant protection against a broad reach of influenza—perhaps as protection to first responders and those at immediate risk, and then as treatment for those infected.”

According to Ramesh Bhatt, Vice President for Research at Sea Lane, “The combination of the team’s innovative antibody library techniques and tremendous scientific rigor enabled the recovery of this extensive collection of antibodies from the avian flu survivors. Because of the large number of antibodies obtained, we were able to perform a detailed immunochemical analysis of these survivors' antibody solutions against avian influenza virus during an actual outbreak.”

The resulting antibody libraries—collections of genetic antibody material—were not dependent on whether an important antibody was being produced by the body at the time of the sample collection. Instead, the scientists were able to obtain the entire immunologic history of an individual’s response, which offered a clearer picture of the relationships between antibodies and their relative effectiveness. These insights may help scientists determine prescient strategies for therapies as the virus mutates in the future.

“Our libraries create a roadmap for improving the efficacy and/or specificity of therapeutic influenza antibodies," Arun Kashyap, Director of Influenza and Antibody Libraries for Sea Lane said. "As a result, we might be able to engineer the best features of different antibodies into a single antibody that may not only treat contemporary strains of influenza, but also future influenza strains which normally would escape through simple mutations.”

Innovative Research Driven by International Effort

“None of this research could have been accomplished without the participation of the Turkish scientists who were responsible for the processes for collection of the bone marrow and their shipment to the laboratories in the United States preserved in a way that made recovery of the antibodies possible. This shows the value of international cooperation in basic scientific research,” said Lawrence Horowitz, CEO of Sea Lane. “Infectious diseases know no national boundaries and treatments will only be developed if the pooled efforts of all scientists are harnessed, regardless of where they happen to reside.”

Source: Scripps Research Institute

Explore further: Antibodies may reveal timing of previous influenza infection

Related Stories

Antibodies may reveal timing of previous influenza infection

August 1, 2017
The amount of influenza-specific antibodies present in an individual's blood can indicate not only if they experienced the flu, but potentially when—a finding that could improve disease monitoring in the tropics, where ...

New DNA-based strategy shows promise against a range of influenza viruses

July 6, 2017
A novel, synthetic, DNA-based strategy to provide protection against a broad array of influenza viruses has been developed in preclinical models by scientists at The Wistar Institute, MedImmune (the global biologics research ...

Researchers develop new method to generate human antibodies

July 24, 2017
An international team of scientists has developed a method to rapidly produce specific human antibodies in the laboratory. The technique, which will be described in a paper to be published July 24 in The Journal of Experimental ...

Microneedle patches for flu vaccination prove successful in first human clinical trial

June 27, 2017
Despite the potentially severe consequences of illness and even death, only about 40 percent of adults in the United States receive flu shots each year; however, researchers believe a new self-administered, painless vaccine ...

New tool demonstrates differences in human immune systems

July 12, 2017
Immune system function varies significantly between individuals, and up to now there has been no effective means of measuring and describing these differences. Now, researchers at Karolinska Institutet have shown that white ...

Researchers to look for bovine influenza antibodies in humans

May 28, 2014
An emerging virus discovered in pigs and later in cows may have affected people without them even knowing it, according to South Dakota State University research assistant professor Natalie Thiex of the biology and microbiology ...

Recommended for you

Researchers describe mechanism that underlies age-associated bone loss

September 22, 2017
A major health problem in older people is age-associated osteoporosis—the thinning of bone and the loss of bone density that increases the risk of fractures. Often this is accompanied by an increase in fat cells in the ...

Researchers develop treatment to reduce rate of cleft palate relapse complication

September 22, 2017
Young people with cleft palate may one day face fewer painful surgeries and spend less time undergoing uncomfortable orthodontic treatments thanks to a new therapy developed by researchers from the UCLA School of Dentistry. ...

Exosomes are the missing link to insulin resistance in diabetes

September 21, 2017
Chronic tissue inflammation resulting from obesity is an underlying cause of insulin resistance and type 2 diabetes. But the mechanism by which this occurs has remained cloaked, until now.

Thousands of new microbial communities identified in human body

September 20, 2017
A new study of the human microbiome—the trillions of microbial organisms that live on and within our bodies—has analyzed thousands of new measurements of microbial communities from the gut, skin, mouth, and vaginal microbiome, ...

Study finds immune system is critical to regeneration

September 20, 2017
The answer to regenerative medicine's most compelling question—why some organisms can regenerate major body parts such as hearts and limbs while others, such as humans, cannot—may lie with the body's innate immune system, ...

Immune cells produce wound healing factor, could lead to new IBD treatment

September 20, 2017
Specific immune cells have the ability to produce a healing factor that can promote wound repair in the intestine, a finding that could lead to new, potential therapeutic treatments for inflammatory bowel disease (IBD), according ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.