Scientists ‘grow’ made-to-order antibodies that can be tailored to treat a range of diseases

The world is facing a crisis. Diseases are mutating and cropping up faster than we can create vaccines for them and clinical trials are time consuming and expensive.

The current method of developing vaccines involves taking samples of the disease and creating an antigen by growing viruses in primary cells, or on continuous cell lines. In the case of human disease, this typically involves taking samples from infected donors and isolating the antigen from the cells used to create it.

Our bodies produce antibodies in B cells to fight infections caused by bacteria, viruses, and other so-called invasive pathogens. When an individual B cell spots an “antigen” molecule that relates to a specific pathogen, it develops plasma cells that release large amounts of the relevant antibody. These antibodies bind to the antigen to battle and effectively kill the infection.

The ideal situation is one where this process is replicated in a lab without the need to take samples from infected donors, yet the most significant barrier to this is the fact that, in addition to encountering a specific antigen, B cells need a second signal to start developing into plasma cells and this is much harder to replicate.

 In the recent study, a team of researchers led by Facundo Batista, from the Francis Crick Institute in London and the Ragon Institute of MGH, MIT, and Harvard, produced specific human antibodies by treating B cells taken from patients with tiny nanoparticles designed to act as this second signal. These nanoparticles mimic the natural process and generate a protein called TLR9 which kickstarts the production of the necessary plasma cells.

This procedure also means cell donors don’t have to have been previously exposed to any of these antigens through vaccination or infection. During tests, the researchers generated anti-HIV antibodies from B cells taken from HIV-free patients, for example.

Since the initial work, the team has successfully used this technique to create various bacterial and viral antigens, including the tetanus toxoid and proteins from several strains of flu. In each case, the researchers produced specific antibodies in “just a few days”. What’s more, some of the anti-influenza antibodies recognised multiple strains of the virus and were able to hinder its ability to infect cells. This could be significant when patients are faced antibiotic resistance, for example, or as viruses mutate and respond to treatment.

“Our work has the potential to evaluate potential immunogenicity in vitro,” Batista told Alphr. “This can be done relatively fast and cheap when compared to clinical trials and could inform about the degree of immunogenicity of different antigens before it goes to the clinic.

Looking to the future, Batista and his colleagues hope that their approach will help researchers rapidly generate therapeutic antibodies for the treatment of infectious diseases and other conditions, such as cancer.

“It is becoming clear that antibodies make excellent drugs,” Batista continued. “Antibodies can protect you from infection or they can serve as a treatment for cancer. The technology developed in this [study] allows for the production of fully human antibodies fast, and in vitro.”

The technique is published in The Journal of Experimental Medicine.

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