Human monoclonal antibodies (mAbs) — highly specific, identical, infection-fighting proteins produced in large quantities in the lab in cell lines that are derived from a single antibody-producing cell — against influenza can be rapidly produced in the lab, according to a new report from scientists supported by the National Institutes of Health (NIH). Using cells drawn from volunteers inoculated with seasonal influenza vaccine, the investigators made influenza-specific mAbs in just a few weeks rather than the typical two to three months. The new technique could potentially be used to rapidly create mAbs for a range of uses, the team says.
Rafi Ahmed, PhD, and Jens Wrammert, PhD, of
The first therapeutic mAb was approved for human use in 1986 and there are now more than 20 Food and Drug Administration-approved mAbs, including two human mAbs, most of which are used to treat certain cancers or immunological diseases. Human mAbs have long been envisioned as possible treatments for acute or chronic infections, but various technical barriers have slowed their development.
"With this new technique for making human monoclonal antibodies efficiently and quickly, Drs. Wilson and Ahmed and their colleagues have made a significant advance," says NIAID director Anthony S. Fauci, MD. "Their accomplishment opens the way to producing mAbs that potentially could be used diagnostically or therapeutically not only for influenza but for other infectious diseases as well."
In addition to being relatively quick to make, the influenza mAbs also bound tightly to virus strains in the seasonal influenza vaccine, the scientists determined. Such high affinity for the vaccine’s viruses suggests that the mAbs would also bind well to the circulating viruses targeted by the vaccine and thus could be used either as a therapy or as a way to diagnose the strain of influenza virus an individual is infected with, say the investigators.
The mAbs made in this study were not tested on influenza virus strains with pandemic potential, such as the H5N1 subtype that causes so-called bird flu. Nevertheless, notes Ahmed, the ability to make high-affinity influenza mAbs quickly raises the possibility of deploying them in combination with other disease control strategies in the event of a global influenza pandemic. According to Ahmed, the group is now planning to use their technique to generate mAbs against H5N1.
To make the new influenza mAbs, the researchers first inoculated volunteers with seasonal influenza vaccine. The scientists wanted to know if a subset of immune system cells called antibody-secreting plasma cells (ASCs) could serve as a source of mAbs. ASCs are the body’s first responders, churning out a surge of antibodies as part of the initial reaction to infection or vaccination. ASC activity is swift but brief. In this study, ASC responses peaked at one week after vaccination, then dropped sharply and were barely detectable after two weeks. The
Wilson and his coworkers at the Oklahoma Medical Research Foundation used the vaccine-generated, influenza-specific ASCs to create the mAbs. Only a few weeks elapsed between vaccination of the volunteers and purification of human mAbs with a high affinity for influenza virus. "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," says Wilson. "In the face of a disease outbreak, the ability to produce infection-fighting human mAbs swiftly would be invaluable."
The technique developed by the
Source: National Institutes of Health (NIH)