|Researchers Find Quick Way to Make Human Monoclonal
Antibodies against Flu
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, Ph.D., and Jens Wrammert, Ph.D., of Emory Vaccine
Center of the School of Medicine, Atlanta, and their coworkers
collaborated with Patrick Wilson, Ph.D., and J. Donald Capra, M.D.,
and others from the Oklahoma Medical Research Foundation, Oklahoma
City. They describe their new method in an advance online publication
in Nature. The research was supported by the NIH’s National
Institute of Allergy and Infectious Diseases (NIAID) and National
Center for Research Resources (NCRR).
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, M.D. "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 Dr. 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 Dr. Ahmed,
the group is now planning to use their technique to generate mAbs
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 Emory University researchers found a way to
capture the fleeting ASCs that produce the initial wave of influenza-specific
antibodies. Importantly, says Dr. Ahmed, as many as 80 percent
of the purified ASCs produced influenza-specific antibodies.
Dr. 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 Dr. 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 Emory University and Oklahoma Medical
Research Foundation scientists is not limited to the production
of mAbs for influenza, and the team is currently working to make
mAbs for other disease agents. "This research holds clinical
potential for a host of infectious diseases including anthrax,
respiratory syncytial virus and pneumococcal pneumonia," says
For more information on information about influenza, visit http://www3.niaid.nih.gov/healthscience/healthtopics/Flu/default.htm.
NIAID is a component of the NIH. NIAID supports basic and applied
research to prevent, diagnose and treat infectious diseases such
as HIV/AIDS and other sexually transmitted infections, influenza,
tuberculosis, malaria and illness from potential agents of bioterrorism.
NIAID also supports research on basic immunology, transplantation
and immune-related disorders, including autoimmune diseases, asthma
News releases, fact sheets and other NIAID-related materials are
available on the NIAID Web site at http://www.niaid.nih.gov.
NCRR, also a component of NIH, provides laboratory scientists
and clinical researchers with resources, tools and training they
need to understand, detect, treat and prevent a wide range of diseases.
NCRR also supports basic, translational and applied research on
variety of diseases through resource building. The research highlighted
here was supported, in part, by NCRR’s Institutional Development
Awards Program, which helps build research infrastructure to enhance
institutions’ research capacity and competitiveness for NIH grants.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.
J Wrammert et al. Rapid cloning of high-affinity human monoclonal
antibodies against influenza virus. Nature DOI: 10.1038/nature06890