June 4, 2007

Human Antibodies Protect Mice from Avian Flu

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An international team of scientists used antibodies from recent human survivors of H5N1 avian influenza to successfully treat and protect mice from H5N1. The technique may one day be used to treat and protect humans from the virus.

The possibility of an influenza pandemic, whether sparked by H5N1 or another flu virus, is a serious public health concern. Dr. Kanta Subbarao and her colleagues at NIH's National Institute of Allergy and Infectious Diseases (NIAID) teamed up with researchers from the Institute for Research in Biomedicine in Bellinzona, Switzerland and the Oxford University Clinical Research Unit at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam to try to develop a therapy for H5N1 based on the immune response of people who'd already survived the virus.

Four Vietnamese adults diagnosed with H5N1 infection between January 2004 and February 2005 agreed to donate blood soon after they had recovered from their illness. The Swiss researchers extracted antibody-producing white blood cells, called memory B cells, from the blood samples and treated them with a process they developed to rapidly and continuously produce large amounts of antibody. Next, researchers in Dr. Subbarao's lab screened 11,000 samples provided by the Swiss team and found a handful that were able to neutralize H5N1 influenza virus in the laboratory. Based on these results, the Swiss researchers purified the B cells and ultimately produced four clones that secrete H5N1-specific neutralizing antibodies (called monoclonal antibodies, or mAbs). Their results were published on May 29, 2007, in PLoS Medicine.

Dr. Subbarao and her coworkers first tested whether the mAbs could protect mice from severe H5N1 infection. All the mice that received one of the H5N1 mAbs tested, regardless of dose, survived, while 80% percent of mice receiving the highest dose of another survived. None of the comparison mice, which were given human mAbs to other pathogens, survived.

The investigators next tested the therapeutic potential of the mAbs. They infected mice with a lethal dose of an H5N1 virus that had circulated in Vietnam in 2004. Groups of mice were then given one of the four H5N1 mAbs at 24, 48 or 72 hours after infection, while another control group received non-influenza mAbs. All the control mice died within 10 days of infection, but 58 of the 60 treated mice survived.

Three of the mAbs also prevented the mice from dying when given 24 hours after they were infected with a related but distinct H5N1 virus. This suggests that human mAbs may provide broad protection against variant H5N1 viruses — an important quality in any therapy aimed at the constantly evolving flu virus.

The researchers next plan to scale up the production of H5N1 mAbs. If the technique proves safe and effective in additional animal tests, they hope to begin evaluating the mAbs in human trials.

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