May 2, 2008 (CIDRAP News) – Technical barriers have prevented the widespread use of human monoclonal antibodies as potent diagnostic and treatment tools, but scientists now say they have found a way to produce antibodies against seasonal influenza much faster than was previously possible.
The researchers, from Emory University in Atlanta and the Oklahoma Medical Research Foundation (OMRF) in Oklahoma City, produced influenza-specific monoclonal antibodies in about a month, rather than the typical 2 to 3 months, using blood from volunteers who had received a seasonal influenza vaccine. They said the new technique could be used to rapidly create monoclonal antibodies for a range of infectious diseases, including pandemic influenza and anthrax.
The scientists released their findings on Apr 30 in a letter in an early online edition of the journal Nature.
Monoclonal antibodies—highly-specific infection-fighting proteins made in a lab in cell lines derived from a single antibody-producing cell—are used to treat some cancers and immunologic diseases.
Only 20 therapeutic monoclonal antibodies have been approved by the US Food and Drug Administration (FDA), and only two of them are from humans, according to an Apr 30 press release from the National Institutes of Health (NIH), which supported the study through the National Institute of Allergy and Infectious Diseases (NIAID) and National Center for Research Resources.
The authors reported that antibody or serum therapy is effective for a wide range of conditions, but the treatments are not widely used because they sometimes cause fatal anaphylactic reactions and serum sickness. "These obstacles can only be overcome by using fully human monoclonal antibodies," they wrote.
In developing the new technique, the researchers explored whether immune system cells called antibody-secreting plasma cells (ASCs) could be used to produce monoclonal antibodies. ASCs play a key role in the initial response to infection or vaccination, the NIH said, but their activity drops sharply and is barely detectable after 2 weeks.
Emory University researchers found a way to capture the ASCs that produce the initial wave of influenza antibodies, the NIH said. A notable finding was that 80% of the purified ASCs produced influenza-specific antibodies, the investigators reported.
In the next phase of the study, researchers from the OMRF used the vaccine-generated, influenza-specific ASCs to create the monoclonal antibodies. After the volunteers were vaccinated, it took researchers only a few weeks to produce a purified human monoclonal antibody that had a high affinity for the influenza virus, the NIH said.
Patrick Wilson, PhD, an immunologist at OMRF, said in the NIH press release, "With just a few tablespoons of blood, we can now rapidly generate human monoclonal antibodies that potentially could be used for diagnosis and treatment of newly emerging strains of influenza. In the face of a disease outbreak the ability to produce infection-fighting human monoclonal antibodies swiftly would be invaluable."
Though the study did not involve a potential pandemic flu strain such as H5N1, Rafi Ahmed, PhD, an immunologist at the Emory Vaccine Center, said in the press release that the team plans to use the technique to generate monoclonal antibodies against the H5N1 virus and other pathogens.
Wrammert J, Smith K, Miller J, et al. Rapid cloning of high-affinity human monoclonal antibodies against influenza virus. Nature 2008; Apr 30 early online publication
Apr 30 NIH press release