Avian influenza survivors' antibodies effective at neutralising H5N1 strain
29 May 2007
Adults who have recovered from the potentially deadly H5N1 strain of avian influenza may hold the key to future treatments for the virus, according to an international team of researchers.
In a study published today in the open access journal 'PLoS Medicine', the researchers have shown how specific antibodies taken from avian flu survivors in Vietnam can be reproduced in the laboratory and prove effective at neutralising the virus in culture vitro and in mice.
The H5N1 influenza virus has caused disease and death in millions of poultry across the globe and occasionally has been transmitted to humans, often fatally. By mid-May 2007, according to the World Health Organization, there had been 306 known cases in humans, 185 of them fatal. 1
Now, doctors based at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam; the Institute for Research in Biomedicine in Bellinzona, Switzerland; and the National Institute of Allergy and Infectious Diseases in Bethesda, USA have shown that monoclonal antibodies 2 generated from blood of human survivors of the H5N1 virus are effective at both preventing infection in mice and neutralising the virus in those already infected. The research had been fast-tracked for funding by the UK's Wellcome Trust and is also supported by grants from the National Institutes of Health in the US and the Swiss National Science Foundation.
The researchers found that the antibodies provided significant immunity to mice that were subsequently infected with the Vietnam strain of H5N1. This reduced significantly the amount of virus found in the lungs and almost completely prevented the virus reaching the brain or spleen. In those people in Vietnam who died from the H5N1 strain, the virus was found to have spread from the lungs; this was not the case in those who survived.
"We have shown that this technique can work to prevent and neutralise infection by the H5N1 'bird flu' virus in mice," says Dr Cameron Simmons, a Wellcome Trust researcher at the Oxford University Clinical Research Unit, Vietnam. "We are optimistic that these antibodies, if delivered at the right time and at the right amount, could also provide a clinical benefit to humans with H5N1 infections."
"In particular, we found that it was possible to administer the treatment up to 72 hours after infection. This is particularly important as people who have become infected with the virus do not tend to report to their local healthcare facilities until several days after the onset of illness."
The antibodies were discovered in the laboratory of Professor Antonio Lanzavecchia at the Institute for Research in Biomedicine in Switzerland. The researchers used a new technique that allows them to rapidly reproduce human monoclonal antibodies starting from a small sample of blood.
"We can't say for certain that a pandemic influenza virus will resemble the H5N1 strain that we have been studying or that the monoclonal antibodies generated using our technique will be able to tackle such a virus," says Professor Lanzavecchia. "Nevertheless, we are encouraged by the broad neutralising activity of these antibodies in the lab and the moderate doses required."
Using administered antibodies has a historical precedent. During the 1918 Spanish H1N1 influenza pandemic, there were multiple reports of physicians administering blood taken from survivors to patients infected with the disease. A recent review suggested that this treatment was associated with a halving in mortality. However, directly administering blood carries a risk of infection with other blood diseases, such as hepatitis C and HIV.
Contact
Craig Brierley
Media Officer
Wellcome Trust
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c.brierley@wellcome.ac.uk
Notes for editors
1. Source: Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO.
2. Monoclonal antibodies are copies of a single antibody that is produced by the body's immune system to recognise and fight a specific infection.
3. Simmons CP et al. Prophylactic and therapeutic efficacy of human monoclonal antibodies against H5N1 influenza. PLoS Med 2007;4(5):e178.
4. The Wellcome Trust is the largest charity in the UK. It funds innovative biomedical research, in the UK and internationally, spending around £500 million each year to support the brightest scientists with the best ideas. The Wellcome Trust supports public debate about biomedical research and its impact on health and wellbeing.
5. The Institute for Research in Biomedicine (IRB) is an independent non-profit research institute founded in Bellinzona, Switzerland in 2000. The eight research groups of the IRB are dedicated to increasing understanding of the mechanisms of host defence against infectious agents, toxins, tumours and neurodegenerative disease. Worldwide rights to the antibody technology have been licensed to Humabs, LLC, a US-based business with offices in Bellinzona.
6. The National Institute of Allergy and Infectious Diseases (NIAID) is a component of the National Institutes of Health. NIAID supports basic and applied research to prevent, diagnose and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections; influenza; tuberculosis; malaria; and illness from potential agents of bioterrorism. NIAID also supports research on basic immunology, transplantation and immune-related disorders, including autoimmune diseases, asthma and allergies.
7. Oxford University's Medical Sciences Division is one of the largest biomedical research centres in Europe. It represents almost one-third of Oxford University's income and expenditure and two-thirds of Oxford University's external research income. Oxford's world-renowned global health programme is a leader in the fight against infectious diseases (such as malaria, HIV/AIDS, tuberculosis and avian flu) and other prevalent diseases (such as cancer, stroke, heart disease and diabetes). Key to its success is a long-standing network of dedicated Wellcome Trust-funded research units in Asia (Thailand, Laos and Vietnam) and Kenya, and work at the MRC Unit in The Gambia. Long-term study of patients around the world is supported by basic science at Oxford and has led to many exciting developments, including potential vaccines for tuberculosis, malaria and HIV, which are in clinical trials.