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Faster Process Devised for Targeted Antibodies

Human B-cell

Human B-cell (NIAID, Flickr)

25 July 2017. Researchers in the U.S. and U.K. designed techniques for quickly generating highly targeted antibodies in the lab, which can speed production of new vaccines and therapies. The team led by Facundo Batista of the Ragon Institute in Cambridge, Massachusetts and Francis Crick Institute in London describes its process in yesterday’s issue of Journal of Experimental Medicine, published by Rockefeller University Press.

Batista and colleagues are seeking better methods for producing antibodies, proteins designed to address specific pathogens such as bacteria or viruses, from human blood samples. Current techniques, say the authors, require extensive screening to find the few, specific B-cells in the immune system that recognize antigen proteins from the pathogen and proliferate into blood plasma cells, which in turn produce antibodies targeting those antigens. These methods, which the team calls laborious, take between 7 and 14 days and often produce just small amounts of antibodies.

The researchers focused on the need for a second trigger to produce antibodies in plasma, beyond the presence of B-cells. This additional trigger is provided by oligonucleotides, short fragments of DNA used routinely today in research, genetic testing and forensics. In this case, a specific type of oligonucleotide stimulates a protein in B-cells called toll like receptor 9, or TLR9, instrumental in generating immune responses. But these oligonucleotides do not discriminate; they generate responses from all B-cells, not just the ones with the target antigen proteins.

As a result, the researchers designed nanoscale particles containing an antigen and oligonucleotide needed to produce antibodies addressing a specific pathogens. The team verified that the process could produce larger quantities of targeted antibodies, and while culturing still took 6 days, it’s still somewhat less time than current methods that provide only small quantities of antibodies.

The researchers tested its antibody production process with tetanus, a few types of influenza, and HIV. The team used blood samples from healthy donors to produce specific antibodies against these infections, including less common influenza strains H5N1 and H7N9, as well as the more common H1N1. The results show some of the influenza antibodies worked with multiple influenza strains and neutralized the viruses before they could cause infections. In addition, the techniques produced HIV antibodies, even though none of the donors had previous exposure to HIV, suggesting a potential new source of vaccines.

The Ragon Institute is a research center affiliated with Massachusetts General Hospital, MIT, and Harvard Medical School developing a vaccine for HIV beginning in 2009. The Francis Crick Institute is an independent medical research center formed by a number of institutions and funding agencies in the U.K. in 2015, addressing the biological underpinnings of  cancer, heart disease, stroke, infections, and neurodegenerative diseases.

In a Rockefeller University Press statement, Batista says the findings should allow for production of therapeutic antibodies, “within a shorter time frame in vitro and without the need for vaccination or blood/serum donation from recently infected or vaccinated individuals. In addition, our method offers the potential to accelerate the development of new vaccines by allowing the efficient evaluation of candidate target antigens.”

Batista is a scientific founder of Blink Therapeutics in Stevenage, U.K., a subsidiary of Blink Biomedical, a developer of synthetic targeted antibodies from B-cells.

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