New insights into how to combat avian flu

Apr 22 2009

An in-depth analysis of blood from patients recovering from the H5N1 avian influenza virus has provided important insights into how to combat the potentially lethal virus.

The findings by U.S. Food and Drug Administration scientists and collaborators better explain what part of the "bird flu" virus is seen by the immune system once a person becomes infected. As one result of this research, a protein of the bird flu virus called PB1-F2 was identified as a potentially potent target for attack by immune systems to stop the spread of the virus.

"Analysis of blood from patients recovering from the H5N1 avian influenza virus can lead to new tools for testing the potential protective activity of vaccines under development," said Karen Midthun, M.D., acting director of the FDA's Center for Biologics Evaluation and Research (CBER). "The findings could also lead to new tests to detect infections, and improved therapies."

Since 2003, more than 400 people worldwide have been infected with the bird flu virus. About 60 percent of them have died. No cases of avian flu have been reported in the United States. Most of the avian flu infections in humans involve people who have had direct contact with infected poultry. However, there is a potential risk for a global influenza pandemic should the virus acquire the ability to spread directly from person to person.

The study, titled "Antigenic Fingerprinting of an H5N1 Avian Influenza Using Convalescent Sera and Monoclonal Antibodies reveals Potential Vaccine and Diagnostic Targets," appears in the April 20, 2009, edition of the online journal PLoS Medicine. http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1000049

The researchers adapted an existing technique using genetically modified viruses (phages) to create a library of fragments representing all of the proteins found in the H5N1 virus. Scientists mixed these fragments with antibodies from five Vietnamese patients recovering from the H5N1 infection and observed which fragments attracted the patient's antibodies.

Several targets that are likely to trigger strong antibody responses to the H5N1 virus were identified, including PB1-F2, a protein that researchers believe contributes significantly to the virus's ability to cause disease.

"We believe this is the first evidence of the human immune system reacting this strongly against PB1-F2," said Hana Golding, Ph.D., chief of CBER's Laboratory of Retrovirus Research and senior author of the article. "This is an indication that it may be a good target for a drug or vaccine."

The study's other authors include first author Surender Khurana, Yonaira Rivera, Jody Manischewitz, and Lisa R. King (FDA); Kanta Subbarao, Amorsolo L. Suguitan Jr. (National Institute of Allergies and Infectious Diseases); Cameron P. Simmons (Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam); and Antonio Lanzavecchia (Institute for Research in Biomedicine, Bellinzona, Switzerland).