 |
|
Scientists identify human monoclonal antibodies effective against bird and seasonal flu viruses
February 23, 2009Researchers at the Dana-Farber Cancer Institute (Dana-Farber), Burnham Institute for Medical Research (Burnham) and the Centers for Disease Control and Prevention (CDC) have reported the identification of human monoclonal antibodies (mAb) that neutralize an unprecedented range of influenza A viruses, including avian influenza A (H5N1) virus, previous pandemic influenza viruses, and some seasonal influenza viruses. These antibodies have the potential for use in combination with other treatments to prevent or treat certain types of avian and seasonal flu. The study was published online on February 22 in Nature Structural and Molecular Biology.
The antibodies identified by the team of scientists neutralize a broad range of influenza A subtypes because they bind to the highly conserved stem region of H5 type hemaglutinin (HA). Binding to the stem prevents a conformational change in the protein that is necessary for viral entry into the host cell, thereby preventing further infection of host cells and the rise of escape mutants.
"The head portion of hemaglutinin is highly mutable, leading to the rise of forms of the virus that can evade neutralizing antibodies," said Robert Liddington, Ph.D., professor and director, Infectious and Inflammatory Disease Center at Burnham and one of the investigators on the study. "However, the stem region of hemaglutinin is highly conserved because it undergoes a dramatic conformational change to allow entry of viral RNA into the host cell. It's very difficult to get a mutation that doesn't destroy that function, which explains why we aren't seeing escape mutants and why these antibodies neutralize such a variety of strains of influenza."
While more costly to produce than existing influenza drugs, therapeutic antibodies can be readily manufactured and stockpiled. In the event of a pandemic, the antibodies could be used in combination with antiviral therapies to contain the outbreak until a vaccine became available. The production of a new influenza vaccine takes six to nine months using conventional methods.
"There are clear settings where human monoclonal antibodies can be used strategically for both the prevention and early treatment of influenza infection and disease," said Wayne A. Marasco, M.D., Ph.D., associate professor of medicine at Dana-Farber and Harvard Medical School. "At-risk individuals, such as first responders and medical personnel, exposed family members and coworkers and patients who cannot make antibodies because of pre-existing medical conditions or advanced age, could all benefit from this new type of therapy."
In the study, the team of scientists used a human antibody phage display library to identify 10 mAb that bind to the stem of H5 type HA, the influenza protein responsible for viral entry into the host cell. The scientists determined the X-ray crystal structure of the mAb bound to the H5N1 HA, which showed that the heavy chain of the mAb inserts into a highly conserved pocket in the HA stem, inhibiting the conformational change required for membrane fusion and viral entry into the cell.
The scientists further showed that an unprecedented number of different types of bird flu and seasonal influenza viruses were inhibited and the mAb protected mice that were exposed to H5N1 virus. "Our human monoclonal antibody protected mice from the lethal H5N1 virus even when injected three days after infection. This is good news, but many antibodies can do this. What surprised us is that the same antibody protected mice from a lethal infection with a very different virus such as the H1N1 subtype that causes seasonal human infections; this is really remarkable," said Dr. Ruben Donis, chief of the Molecular Virology and Vaccines Branch at CDC.
Vaccines consisting of attenuated or killed virus do not typically stimulate antibodies against the stem, perhaps because it is less accessible than the head region. In this study, the scientists used recombinant purified protein, not virus, so the antigenic part of the virus recognized by the antibodies was fully exposed.
Seasonal influenza occurs each year, causing mild to severe illness. Worldwide, more than 250,000 deaths from seasonal influenza occur annually. The best protection from seasonal influenza is yearly vaccination.
Influenza pandemics are worldwide outbreaks of disease that occur when a new influenza virus emerges for which people have little or no immunity. The disease spreads easily person-to-person, causes serious illness, and can spread across the country and around the world in a very short time. Health professionals are concerned that the continued spread of a highly pathogenic avian influenza A (H5N1) virus across eastern Asia and other countries represents a significant threat to human health. While vaccines can control influenza, they are not always effective because the vaccine must be updated each year. Vaccines against H5N1 in development have shown promise, but none has been reported to elicit a broad response in humans that would cover a broad range of different H5N1 virus strains. Antiviral medications, including the neuraminidase inhibitor oseltamivir (Tamiflu ®), is the primary treatment method, but has limited effectiveness if administered more than 24-48 hours after symptom onset.
Burnham Institute
While more costly to produce than existing influenza drugs, therapeutic antibodies can be readily manufactured and stockpiled. In the event of a pandemic, the antibodies could be used in combination with antiviral therapies to contain the outbreak until a vaccine became available. The production of a new influenza vaccine takes six to nine months using conventional methods.
"There are clear settings where human monoclonal antibodies can be used strategically for both the prevention and early treatment of influenza infection and disease," said Wayne A. Marasco, M.D., Ph.D., associate professor of medicine at Dana-Farber and Harvard Medical School. "At-risk individuals, such as first responders and medical personnel, exposed family members and coworkers and patients who cannot make antibodies because of pre-existing medical conditions or advanced age, could all benefit from this new type of therapy."
In the study, the team of scientists used a human antibody phage display library to identify 10 mAb that bind to the stem of H5 type HA, the influenza protein responsible for viral entry into the host cell. The scientists determined the X-ray crystal structure of the mAb bound to the H5N1 HA, which showed that the heavy chain of the mAb inserts into a highly conserved pocket in the HA stem, inhibiting the conformational change required for membrane fusion and viral entry into the cell.
The scientists further showed that an unprecedented number of different types of bird flu and seasonal influenza viruses were inhibited and the mAb protected mice that were exposed to H5N1 virus. "Our human monoclonal antibody protected mice from the lethal H5N1 virus even when injected three days after infection. This is good news, but many antibodies can do this. What surprised us is that the same antibody protected mice from a lethal infection with a very different virus such as the H1N1 subtype that causes seasonal human infections; this is really remarkable," said Dr. Ruben Donis, chief of the Molecular Virology and Vaccines Branch at CDC.
Vaccines consisting of attenuated or killed virus do not typically stimulate antibodies against the stem, perhaps because it is less accessible than the head region. In this study, the scientists used recombinant purified protein, not virus, so the antigenic part of the virus recognized by the antibodies was fully exposed.
Seasonal influenza occurs each year, causing mild to severe illness. Worldwide, more than 250,000 deaths from seasonal influenza occur annually. The best protection from seasonal influenza is yearly vaccination.
Influenza pandemics are worldwide outbreaks of disease that occur when a new influenza virus emerges for which people have little or no immunity. The disease spreads easily person-to-person, causes serious illness, and can spread across the country and around the world in a very short time. Health professionals are concerned that the continued spread of a highly pathogenic avian influenza A (H5N1) virus across eastern Asia and other countries represents a significant threat to human health. While vaccines can control influenza, they are not always effective because the vaccine must be updated each year. Vaccines against H5N1 in development have shown promise, but none has been reported to elicit a broad response in humans that would cover a broad range of different H5N1 virus strains. Antiviral medications, including the neuraminidase inhibitor oseltamivir (Tamiflu ®), is the primary treatment method, but has limited effectiveness if administered more than 24-48 hours after symptom onset.
Burnham Institute
Influenza Current Events and Influenza News RSSU.S. and European Experts Applaud Creation of New Transatlantic Task Force on Global Antibiotic Resistance Threat
Experts on both sides of the Atlantic applaud President Barack Obama and Swedish Prime Minister Fredrik Reinfeldt, representing the European Union (EU) Presidency, for establishing a transatlantic task force to address antibiotic resistance, an urgent and growing problem that threatens patient safety and public health worldwide.
Poll: Many parents, high-priority adults who tried to get H1N1 vaccine unable to get it
A new national poll from Harvard School of Public Health (HSPH) researchers found that a majority of adults who tried to get the H1N1 vaccine for themselves or their children have been unable to do so.
When should flu trigger a school shutdown?
As flu season approaches, parents around the country are starting to face school closures. But how bad should an influenza outbreak be for a school to shut down?
Common Pain Relievers May Dilute Power of Flu Shots
With flu vaccination season in full swing, research from the University of Rochester Medical Center cautions that use of many common pain killers - Advil, Tylenol, aspirin - at the time of injection may blunt the effect of the shot and have a negative effect on the immune system.
There's a speed limit to the pace of evolution, Penn biologists say
Researchers at the University of Pennsylvania have developed a theoretical model that informs the understanding of evolution and determines how quickly an organism will evolve using a catalogue of "evolutionary speed limits."
Initial Results Show Pregnant Women Mount Strong Immune Response To One Dose of 2009 H1N1 Flu Vaccine
Healthy pregnant women mount a robust immune response following just one dose of 2009 H1N1 influenza vaccine, according to initial results from an ongoing clinical trial sponsored by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health.
Flu vaccine given to women during pregnancy keeps infants out of the hospital
Infants born to women who received influenza vaccine during pregnancy were hospitalized at a lower rate than infants born to unvaccinated mothers.
Pandemic flu vaccine campaigns may be undermined by coincidental medical events
The effectiveness of pandemic flu vaccination campaigns - like that now underway for H1N1 - could be undermined by the public incorrectly associating coincidental and unrelated health events with the vaccines.
Scientists discover influenza's Achilles heel: Antioxidants
As the nation copes with a shortage of vaccines for H1N1 influenza, a team of Alabama researchers have raised hopes that they have found an Achilles' heel for all strains of the flu-antioxidants.
NIAID scientists propose new explanation for flu virus antigenic drift
Influenza viruses evade infection-fighting antibodies by constantly changing the shape of their major surface protein.
More Influenza Current Events and Influenza News Articles
 |
The Great Influenza: The story of the deadliest pandemic in history by John M. Barry (Author) At the height of WWI, history’s most lethal influenza virus erupted in an army camp in Kansas, moved east with American troops, then exploded, killing as many as 100 million people worldwide. It killed more people in twenty-four months than AIDS killed in twenty-four years, more in a year than the Black Death killed in a century. But this was not the Middle Ages, and 1918 marked the first collision of science and epidemic disease. Magisterial in its breadth of perspective and depth of research and now revised to reflect the growing danger of the avian flu, The Great Influenza is ultimately a tale of triumph amid tragedy, which provides us with a precise and sobering model as we confront the epidemics looming on our own horizon. John M. Barry has written a new ... |
 |
A Cruel Wind: Pandemic Flu in America 1918-1920 by Dorothy A. Pettit (Author) The flu pandemic that began in 1918 touched with illness virtually every family in America. It was a devastating time, far overshadowing the carnage of World War I as the pandemic killed more people in less time than any disease before or since. With 25% to 30% of the worlds population having clinically apparent illnesses and a mortality rate of 2.5% - 5%, it is believed that more than 675,000 Americans were among the 50-100 million that died worldwide. Because many experts believe that it is not a matter of if the world will encounter another 1918-like flu pandemic, but when, this social history of the pandemic should be considered essential reading for students, public health officials, doctors, nurses, journalists, and those in government office, interested in learning what workedand... |
 |
Flu : The Story Of The Great Influenza Pandemic by Gina Kolata (Author) A scientific history of the Great Flu Epidemic of 1918, which killed at least 40 million people. The author details the science and latest understanding of flu, examines the chances of a great epidemic recurring and explores what can be done to prevent it. |
 |
Flu: A Social History of Influenza by Tom Quinn (Author) It may sound innocuous compared to war, plague and famine, but flu is in fact one of the world's biggest killers. Strains of the virus are always in circulation but every so often a new and particularly virulent one comes along, to which we have no historic immunity - when that happens the consequences are devastating. This fascinating book explores the havoc caused by the world's most deadly virus - and the destruction left in its wake. From its initial identification by the Greek physician Hippocrates in the 4th century BC to the Spanish flu pandemic of 1918 and beyond, Tom Quinn explores the social, medical and scientific ramifications of the major outbreaks that have occurred over the centuries - and the potential consequences should such a pandemic occur in the modern world, an event... |
 |
American Experience - Influenza 1918 Starring: David McCullough, David Ogden Stiers, Joe Morton, Linda Hunt, Will Lyman Also With: Katy Mostoller (Producer), Michael Rossi (Producer), Rocky Collins (Producer), Rocky Collins (Writer), Tracy Heather Strain (Producer), Henry Hampton (Writer) As the nation mobilized for war in the spring of 1918, ailing Private Albert Gitchell reported to an army hospital in Kansas. He was diagnosed with the flu, a disease about which doctors knew little. Before the year was out, America would be ravaged by a flu epidemic that killed 675,000 people--more than died in all the wars of this century combined--before disappearing as mysteriously as it began. |
 |
The Devil's Flu: The World's Deadliest Influenza Epidemic and the Scientific Hunt for the Virus That Caused It by Pete Davies (Author) A gripping account of the 1918 flu pandemic and the modern-day hunt for this elusive and deadly virus In 1918, a flu virus more lethal than any that has come along since swept through the world, from the remotest villages in Arctic climates to crowded U.S.cities to the battlefields of Europe, killing forty million people. Yet, despite its devastating toll and the probability that other deadly pandemics await on the horizon, it was relegated to a footnote in history. The Devil's Flu is the extraordinary story of 1918's forgotten tragedy and of the global scientific community's effort to avert another such disaster. The 1918 flu still so intrigues and frightens experts in the field that in 1998, a group of respected scientists journeyed to the Norwegian Arctic Circle in search... |
 |
Influenza Virology: Current Topics by Yoshihiro Kawaoka (Author) |
 |
Rapid Reference to Influenza by Jan Wilschut (Author), Janet Mcelhaney (Author), Abraham Palache (Author) Provides the reader with authoritative and accessible information on the subject of influenza. Clearly written by key experts in the field and highly illustrated in full colour, the book provides an overview of influenza, its pathogenesis, epidemiology, the burden of disease and its health economics. Rapid Reference Influenza also summarises available information on the molecular biology of influenza and the emergence of new influenza viruses. Completely updated with the latest information on H5N1, the book aims to contribute to international efforts to emphasize the major burden of influenza and the need for better control. * Expert information succinctly written for ease of use. * Abundant use of bulleted lists and short tables, for quick access to comparative information. * Presents... |
 |
H1N1 and Swine Influenza (Flu) Protection Kit w/ N95 Masks - Meets CDC Guidelines for H1N1 and Swine Flu by JIB EDP Protect against all Influenza's (Flu) Help protect yourself and your family with this Flu Defense Kit. The masks contained in the kit are N95 rated and meet guidelines set forth by the CDC and the Department of Health and Human Services for influenza (flu) protection. In addition to this kit, you MUST: Stay informed. - Influenza is thought to spread mainly person-to-person through coughing or sneezing of infected people. - Take everyday actions to stay healthy. -Cover your nose and mouth with a tissue when you cough or sneeze. Throw the tissue in the trash after you use it. - Wash your hands often with soap and water, especially after you cough or sneeze. Alcohol-based hands cleaners are also effective. - Avoid touching your eyes, nose or mouth. Germs spread that way. - Stay home... |
 |
America's Forgotten Pandemic: The Influenza of 1918 by Alfred W. Crosby (Author) Between August 1918 and March 1919 the Spanish influenza spread worldwide, claiming over 25 million lives, more people than those perished in the fighting of the First World War. It proved fatal to at least a half-million Americans. Yet, the Spanish flu pandemic is largely forgotten today. In this vivid narrative, Alfred W. Crosby recounts the course of the pandemic during the panic-stricken months of 1918 and 1919, measures its impact on American society, and probes the curious loss of national memory of this cataclysmic event. In a new edition, with a new preface discussing the recent outbreaks of diseases, including the Asian flu and the SARS epidemic, America's Forgotten Pandemic remains both prescient and relevant. Alfred W. Crosby is a Professor Emeritus in American Studies,... |
| © 2009 BrightSurf.com |