Using antibodies derived from immune cells from recent human survivors of H5N1 avian influenza to successfully treat H5N1-infected mice as well as protect them from an otherwise lethal dose of the virus, revealed by researchers.
An international team of scientists, including researchers from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, conducted the study to prepare the medicines and vaccines against human bird flu.
“The possibility of an influenza pandemic, whether sparked by H5N1 or another influenza virus to which humans have no natural immunity, is of serious concern to the global health community,” says NIAID Director Anthony S. Fauci, M.D. “If the success of this initial study is confirmed through further laboratory and clinical trials, human monoclonal antibodies could prove to be valuable therapeutic and prophylactic public health interventions for pandemic influenza.”
The research, to be published May 29 in PLoS Medicine, represents a three-way collaboration among Kanta Subbarao, M.D., and her coworkers at NIAID; Antonio Lanzavecchia, M.D., and colleagues from the Institute for Research in Biomedicine, Bellinzona, Switzerland; and Cameron Simmons, Ph.D., from the Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
Four Vietnamese adults diagnosed with H5N1 influenza infection between January 2004 and February 2005 agreed to donate blood soon after they had recovered from their illness. In Switzerland, Dr. Lanzavecchia extracted antibody-producing white blood cells, called memory B cells, from the Vietnamese samples.
Next, researchers in Dr. Subbarao’s lab screened 11,000 antibody-containing samples provided by the Swiss team and found a handful able to neutralize H5N1 influenza virus. Based on these results, Dr. Lanzavecchia purified the B cells and ultimately created four monoclonal antibodies (mAbs) that secrete H5N1-specific neutralizing antibodies.
Dr. Subbarao and her coworkers first tested whether the human H5N1 mAbs could protect mice from severe H5N1 infection. Groups of five mice received either of two human H5N1 mAbs at one of three dosages or human mAbs against diphtheria or anthrax. One day later, the mice were exposed through their noses to lethal doses of H5N1 influenza virus.
All the control mice?those receiving non-H5N1 mAbs?rapidly developed severe illness and died within a week. In contrast, all the mice that received the first H5N1 mAb tested?regardless of dose?survived, while 80 percent of mice receiving the highest dose of the second H5N1 mAb survived.
Using blood products from influenza survivors is an old idea, the researchers note. During the flu pandemic of 1918-19, for example, physicians took serum from recovered flu patients and gave it to new victims; recent historical research indicates that those blood transfusions, when given early in the illness, sometimes saved recipients’ lives.