An international team of scientists has shown that specific antibodies taken from the blood of Vietnamese survivors of the deadly strain of H5N1 avian flu can be reproduced in the laboratory and used to neutralize the virus in a test tube and in mice, suggesting that it could also be a way to confer immunity to humans before and shortly after becoming infected.

The findings are published in the open access journal PLoS Medicine.

The study was supported by the UK"e;s Wellcome Trust (via fast-track funding), and grants from the US National Institutes of Health and the National Science Foundation in Switzerland.

Researchers working 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, US, took monoclonal antibodies from the blood of human survivors of the deadly strain of H5N1 avian flu virus and proved that it neutralizes the virus in infected mice and prevents the virus from infecting mice that do not yet have the disease.

Influenza outbreaks affect millions of people every year, and kill about half a million all over the world. Those who recover do so because their immune system learns to make antibodies against the new virus that eventually overwhelm and neutralize it. However, the influenza virus has a habit of mutating into new strains, so the next time flu is in your area there is no guarantee that the antibodies you made when you had it last time will work this time.

Epidemics break out because now and again the virus is so different than nobody"e;s antibodies work, and neither do vaccines, which are always, by definition, one step behind because they are developed from the old strain.

The deadly strain of H5N1 has killed millions of birds around the world and in some rare instances it has also spread from bird to human. Of the 306 human cases reported to the World Health Organization, 185 resulted in death, a mortality rate of 60 per cent, which is much much higher than the more common annual flu or less deadly strains of H5N1 that can also pass from bird to human, as one did recently in Wales, UK.

So far the deadly strain of H5N1 has not acquired the ability to spread from human to human, but many experts believe that one day it will, and when that happens there will be a worldwide pandemic because apart from the one hundred or so survivors of this deadly strain, nobody has antibodies against it and the vaccines are already falling behind.

Scientists are therefore always on the lookout for ways to keep up with the virus and its mutations.

One way to do this is to use the antibodies of survivors of the current strain, as an epidemic unfolds. This is reported to have happened in the 1918 Spanish H1N1 influenza pandemic, where doctors took blood from survivors and administered it to infected patients. Recent research suggests this may have halved the death rate. However, there are many risks doing it this way because of the other infectious agents that could be in the blood of the donor such as hepatitis C and HIV.

In this latest study, researchers isolated and "immortalized" a range of immune cells from the blood of the H5N1 survivors. Then they took each cell and extracted the specific monoclonal antibodies that they made and tested their ability to neutralize H5N1, plus some other flu viruses, one by one, in test tubes.

They identified which monoclonal antibodies neutralized the exact H5N1 strain that the donor patients had been infected with and tested them again, this time against some closely related strains of H5N1 and one from a different lineage (clade) also known to have infected humans. The antibodies showed some ability to neutralize all the strains, but in some cases the effect was stronger than others.

The researchers then tested the antibodies on mice infected with the original strain of H5N1 that had infected the donor survivors. They found the antibodies were effective both at preventing infection (when given the day before infection) and after infection (when given up to 72 hours later).

They also found that three of the antibodies gave the mice partial immunity against H5N1 from a different clade.

The effect of the antibodies was to limit the ability of the virus to reproduce and damage the lungs, as well as spread from the lungs to other parts of the body, such as the brain and spleen. In the Vietnamese victims who died from the deadly H5N1 strain the virus was found to have spread from the lungs, whereas it had not in the survivors.

Dr Cameron Simmons, a Wellcome Trust researcher at the Oxford University Clinical Research Unit, Vietnam, and co-author of the study said:

"We have shown that this technique can work to prevent and neutralize infection by the H5N1 "e;bird flu"e; virus in mice."

"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," he added.

Simmons went on to explain the benefit of being able to administer 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."

In this particular study the researchers used a new method that very quickly reproduces human monoclonal antibodies starting with just a small sample of blood. The work was done by scientists working in the laboratory of Professor Antonio Lanzavecchia at the Institute for Research in Biomedicine in Switzerland.

"We can"e;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," said Lanzavecchia.

However, he said the team was greatly encouraged by the "broad neutralizing activity of these antibodies in the lab and the moderate doses required".

According to the accompanying editorial, this study shows that large amounts of pure monoclonal antibodies could be made quite easily, using the new method. The study also shows that a group of antibodies derived from one strain will provide protection against a range of different clades.

However, the editorial draws attention to the authors"e; own note of caution which emphasizes the need to test any antibodies derived in this way against emerging pandemic versions because they could be genetically quite different.

"Prophylactic and Therapeutic Efficacy of Human Monoclonal Antibodies against H5N1 Influenza."
Cameron P. Simmons, Nadia L Bernasconi, Amorsolo L Suguitan Jr, Kimberly Mills, Jerrold M Ward, Nguyen Van Vinh Chau, Tran Tinh Hien, Federica Sallusto, Do Quang Ha, Jeremy Farrar, Menno D de Jong, Antonio Lanzavecchia, Kanta Subbarao.
PLoS Medicine Vol. 4, No. 5, e178
doi:10.1371/journal.pmed.0040178

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Written by: Catharine Paddock
Writer: Medical News Today
Copyright: Medical News Today