A study, published in Nature Structural and Molecular Biology, says that the “llama-based, COVID-19-specific ‘antibody cocktail’ could enter clinical trials within months”.
The researchers conducting the study, from the UK’s Rosalind Franklin Institute, have been studying Fifi’s (a llama in Reading, UK) specially evolved antibodies to make an immune-boosting therapy for quite some time now.
Coronavirus: Llamas provide key to immune therapy https://t.co/Z2jHgOOCiq
— BBC Science News (@BBCScienceNews) July 13, 2020
The study included “engineering” llama antibodies, considerably small, and exhibit a simplified structure relative to the antibodies found in human blood. That simple size and structure means they can be “redesigned” in the lab.
Professor James Naismith, director of the Rosalind Franklin Institute – and the lead author of the study, explained the techniques, “With the llama’s antibodies, we have keys that don’t quite fit – they’ll go into the lock but won’t turn all the way round. So, we take that key and use molecular biology to polish bits of it, until we’ve cut a key that fits.”
The SARS-CoV-2 virus can spread widely and is more transmissible than previously reported coronaviruses, causing a more serious illness than influenza. The SARS-CoV-2 receptor binding domain (RBD) of the spike protein binds to the human angiotensin-converting enzyme 2 (ACE2) receptor as a prelude to viral entry into the cell. The use of this technology, naive llama single-domain antibody library and PCR-based maturation, the researchers synthesized two very small nano-antibodies, similar to human antibodies, that are capable of blocking virus interaction with the ACE2 receptor.
In the study, the use of techniques called a “Single-particle cryo-EM” revealed that both nanobodies bind to all three RBDs in the spike trimer. The scientists were able to study the crystal structures of each “nanobody–RBD complex”, which explained how they interact with each other.
Antibodies are an integral part of the adaptive immune system, that protect from serious pathogens such as viruses and bacteria and give the individuals long term protection by remembering the pathogens from their first encounter, to remain vigilant in case of re-exposure to the pathogens. This is explained by Prof Naismith, “Then if you get re-infected, your body looks for any [virus particles] with antibodies stuck around them and destroys them.”
Therefore, it is vital to develop this particular type of immune therapy, particularly to improve immune system of a sick person with the help of antibodies which have already adapted to the virus. Reports have been coming, giving an evidence of antibody-rich blood, taken from people who have recently recovered from the coronavirus, could be used as a treatment. But the key trick with this llama-derived antibody therapy is that the scientists can produce coronavirus-specific antibodies to order.
This work establishes that nanobody maturation technology can be deployed to produce a highly neutralizing agent against an emerging viral threat in real time. The approach may be useful in identifying complementary epitopes to those identified by animal immunization approaches. The small nanobodies may find application in a cocktail of laboratory-synthesized neutralizing antibodies given for passive immunization of severely ill COVID-19 patients.