CAJICA, Colombia – A team of scientists in Argentina is working on obtaining monoclonal antibodies from hens and llamas in a bid to produce both a vaccine and a drug for SARS-CoV-2, but the development process is highlighting the challenges that researchers and scientists in developing countries with troubled economies can face.
The team is betting that antibodies obtained from llamas may be used to develop a vaccine as well as a drug for COVID-19 patients, but to get its products into the clinic it will have to overcome top-heavy bureaucracies and shortages of funds and will have to use grants that are worth much less today than they were just a couple of months ago.
“The idea is to administer [vaccines and treatments] through misting, to prevent infections in the case of high risk or exposed patients, and also, in cases [when patients have] been diagnosed and the virus is infecting the airways and the throat,” Viviana Parreño, scientific coordinator at the platform for the development of tech projects from the National Institute of Agricultural Technology (INCUINTA) in Argentina, told BioWorld. “The idea is to administer them so the virus becomes unable to reach the lungs.
The team at INCUINTA shifted its priorities as soon as the COVID-19 pandemic emerged.
“Right when the outbreak started, we were working on bovine coronavirus and since we had this experience and we had developed strategies for vaccines, and using yolks as well, we knew we could start immediately working in a human coronavirus, because we´ve got the expertise of multiplying the virus,” said Parreño.
Parreño´s team is working around the clock to obtain single-domain antibodies out of the llamas that react against SARS-CoV-2. The researchers at INCUINTA are basing their project on their previous experience developing antibodies against rotavirus and norovirus, on which they have been working since 2005.
“We already saw that this technology could be applied to human health, and this first antibody that we developed [makes it possible] to neutralize all the variants of the rotavirus that produce diarrhea and we really want this product to hit the market,” said Parreño.
“We then did another project for norovirus, which is the second viral agent that produces diarrheas related to food poisoning, and we were right in the interim of transferring the technologies to a company to produce the antibodies against these viruses and the outbreak hit,” she said.
Those projects, and the tech transfers related to them, were put on hold and the team shifted to producing antibodies out of llamas and hens to fight COVID-19, something that is also being done with other type of camelids in places like Belgium and in Austin, Texas.
“A research group in Belgium led by immunologists in the nineties, discovered that camelids, the dromedaries and also llamas, have this special type of antibodies, from which you can take a part and express it into a recombinant protein which has the characteristic of being monoclonal and recombinant,” she explained.
From that discovery, Belgian researchers founded Ablynx NV, based in Ghent, Belgium.
“In 2018, they launched their first product into the market, and we believe it will revolutionize the whole industry of monoclonal antibodies,” said Parreño.
Help from abroad
Thousands of miles away from Belgium, and using their own native South American camelids, Parreño’s team expects to obtain monoclonal antibodies to fight COVID-19.
The team at INCUINTA has already administered three doses of a designed protein to five specimens of llamas. On June 25, the researchers will administer the fourth and last dose. Afterward, they expect to start obtaining the antibodies.
“We wanted to immunize with the deactivated virus, but we didn't obtain the permits,” said Parreño.
Even though Argentina’s Ministry of Health did not grant permits to the team to use the live virus, the team was able to move forward expressing a protein thanks to Karin Bok, an Argentine who is senior advisor for vaccine development at the Vaccine Research Center (VRC), from the U.S. NIH at Bethesda, Md.
“She gave us the plasmids of the vaccine that the U.S. is trying nowadays, and with these plasmids, we expressed the protein to immunize the llama, and we expect to be able soon to obtain the antibodies for COVID-19,” said Parreño.
The contribution of the NIH helped Parreño’s team to move forward in immunizing the camelids, but the team is also running the plasmids against its own library of nano antibodies used for bovine coronaviruses.
“Some clones have resulted positive, and we’ve sent them to sequencing and we are very anxiously waiting for those results,” said Parreño.
A vast network of Argentines abroad is supporting the project. One has linked INCUINTA with Virginia Tech in Blacksburg, Va., which is now involved in the project.
“We are going to run the preclinical models at Virginia Tech with mice and hamsters,” said Parreño. “What is important here is to know, for one part, that it is in fact going to protect against the infection, and, on the other, to demonstrate that those antibodies don't produce side effects as the inflammatory cascades and other side effects that sometimes the immune system generates,” she explained.
According to Parreño, it is easier to run preclinical trials in the U.S., where scientists already have the model in place.
Moreover, the harsh economic situation faced by Argentina makes it difficult for scientists to find the resources they need and even reactive agents.
“If you want to make an assay right, you spend five plates, but you have only reactive agents for one, so you have to think all the time how to assemble the trial, while saving reactive agents,” said Parreño.
The team at INCUINTA applied for a grant from the Argentine government. At the time of the application, the grant was worth about $100,000 in Argentine pesos (about US$1,436). Two months later, due to inflation and currency devaluation, the grant is worth just $60,000. Parreño estimates that at least $300,000 will be needed to keep the project alive and move to the preclinical trial phase.
If the team succeeds in overcoming the financial and logistical challenges, it expects to start working with humans by the end of the year.