Treating patient derived B cells with nanoparticles coated with CpG oligonucleotides to stimulate plasma cell production and challenge antigens to designate what kind of antibody the B cells should produce has resulted in the generation of specific, high affinity antibodies in just a few days that can recognize several strains of a pathogen at the same time. The researchers have already produced antibodies to a variety of bacterial and viral antigens, including tetanus toxoid and several strains of influenza, and were able to generate anti HIV antibodies from B cells donated by healthy volunteers who did not have the disease.
The new technique also eliminates the need for previous exposure to the pathogens, either by vaccination or infection.
"Our technique should allow the production of these antibodies within a shorter time frame in vitro and without the need for vaccination or blood/serum donation from recently infected or vaccinated individuals," said Dr. Facundo Batista, who led the team from the Francis Crick Institute in London, the Ragon Institute of Massachusetts General Hospital, MIT and Harvard. "In addition, our method offers the potential to accelerate the development of new vaccines by allowing the efficient evaluation of candidate target antigens."
Antibodies are produced by white blood cells called B cells, which recognize the calling card of a bacteria or virus called an antigen, and transform into plasma cells tailored to produce large numbers of antibodies to that specific antigen that fight off the disease. That's what happens in the body. When scientists tried to reproduce the process in the lab, they ran into problems getting the B cells to make the specific kind of plasma cells they needed because the challenge antigens were missing.
It was easy to get the B cells to proliferate by adding short DNA fragments called CpG oligonucleotides into their culture medium. CpG oligonucleotides activate a protein inside B cells TLR9, but TLR9 enthusiastically stimulates every B cell in the sample to respond, not just the tiny fraction capable of producing a particular antibody. Batista and his colleagues attached both CpG oligonucleotides and real challenge antigens to nanoparticles, added them to B cell cultures, and the plasma cells that resulted were both abundant and pathogen specific.
The team hopes their approach will help researchers produce therapeutic antibodies to treat infectious disease and other conditions, such as cancer.
For more information, go to the Journal of Experimental Medicine
http://jem.rupress.org/cgi/doi/10.1084/jem.20170633?PR
https://www.eurekalert.org/pub_releases/2017-07/rup-rdn071717.php
The new technique also eliminates the need for previous exposure to the pathogens, either by vaccination or infection.
"Our technique should allow the production of these antibodies within a shorter time frame in vitro and without the need for vaccination or blood/serum donation from recently infected or vaccinated individuals," said Dr. Facundo Batista, who led the team from the Francis Crick Institute in London, the Ragon Institute of Massachusetts General Hospital, MIT and Harvard. "In addition, our method offers the potential to accelerate the development of new vaccines by allowing the efficient evaluation of candidate target antigens."
Antibodies are produced by white blood cells called B cells, which recognize the calling card of a bacteria or virus called an antigen, and transform into plasma cells tailored to produce large numbers of antibodies to that specific antigen that fight off the disease. That's what happens in the body. When scientists tried to reproduce the process in the lab, they ran into problems getting the B cells to make the specific kind of plasma cells they needed because the challenge antigens were missing.
The team hopes their approach will help researchers produce therapeutic antibodies to treat infectious disease and other conditions, such as cancer.
For more information, go to the Journal of Experimental Medicine
http://jem.rupress.org/cgi/doi/10.1084/jem.20170633?PR
https://www.eurekalert.org/pub_releases/2017-07/rup-rdn071717.php
