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Designing Nanobodies for Viral Pandemics with Alpacas

byZEISS Microscopy 6 April 2023 3 min read

Introduction

Designing Nanobodies for Viral Pandemics with Alpacas

High content microscopy used to screen nanobodies designed for emerging infectious diseases

Therapeutic monoclonal antibody drugs provide effective treatment for an expanding list of human afflictions, from many cancers to autoimmune, metabolic, and infectious diseases. Some scientists are researching what is possibly the next best antibody drug – nanobodies.

Dr. Alejandro Rojas-Fernandez is an Assistant Professor at Austral University, Chile. In 2017, he formed his lab with the purpose of developing a system to produce recombinant nanobodies against emerging infectious diseases. Less than three years later, their platform was challenged with the COVID-19 pandemic. In their first publication, they show how a simple, cost-effective method successfully generated nanobodies to SARS-CoV-2 within just a few months, verifying nanobody efficacy with biochemistry and high content microscopy using ZEISS Celldiscoverer 7.

Dr. Alejandro Rojas-Fernandez with one of his nanobody generating alpacas

Alpaca Nanobodies to Combat Emerging Viruses

Nanobodies are lab-generated antibodies that originate in camelids, which include alpacas. They are significantly smaller in size compared to monoclonal antibody drugs, which means they can penetrate tissues easier and access previously inaccessible regions, thereby expanding drug developers access to a higher number of potential therapeutic targets. They are also easier and cheaper to manufacture.

In his home country of Chile, Dr. Rojas-Fernandez saw a unique opportunity to build a research group focused on generating recombinant nanobodies against emerging viruses using native alpaca herds, which are native to his country.

Janine Burkhalter, student from the University of Konstanz, Germany and DAAD RISE program fellow working at ZEISS Celldiscoverer 7 in Dr. Rojas-Fernandez's lab

Creating a Platform for Emergent Virus Preparedness

In 2017, Dr. Rojas-Fernandez and his team were awarded a local scientific grant by FICR for “generation of a platform for the preparedness for emergent virus infections” and purchased ZEISS Celldiscoverer 7 and a PAA robotic system with part of the funding. Their focus at that time was the generation of nanobodies against hantaviruses, not expecting that a global pandemic would emerge in 2020 and challenge their platform to generate nanobodies against SARS-CoV-2.

By May 2020, Dr. Rojas-Fernandez and his team had characterized a very powerful neutralizing nanobody called W25, described in their publication. Currently, they have a preprint showing that W25 demonstrates favorable preclinical properties and should be pursued for further clinical development. This work is in tight collaboration with Dr. Daniel Watterson, University of Queensland, Australia.

We used the ZEISS Celldiscoverer 7 high content microscopy system day and night until we got the neutralizing nanobodies against Covid-19 that we were looking for. Unexpectedly, we became one of the first groups worldwide to describe neutralizing nanobodies against the virus, and our strategy since then is to use high content microscopy for every nanobody we develop. Our capabilities today are very high, we can screen 100x 384-well plates in 7 channels, fully automated.

Dr. Alejandro Rojas-Fernandez Assistant Professor, Austral University, Chile

Control HeLa cells stained with DAPI (blue) and anti-tubulin antibody (red) and imaged with ZEISS Celldiscoverer 7. — Control HeLa cells stained for DAPI (blue) with anti-tubulin antibody (red) and imaged with ZEISS Celldiscoverer 7.

Diagnostics and treatments for COVID-19 and more

Dr. Rojas-Fernandez and his team have now patented 30 nanobodies that target SARS-CoV-2 and are working to develop drugs from the nanobodies to treat COVID-19.

In addition, they are also working with collaborators to generate targeted nanobodies to other viruses such as Nipah, Hendra, Lassa, Ebola, and many different members of the Flavivirus family. Their goal is to generate an emergency toolkit with therapies for the most dangerous viruses to prepare us in case of a new pandemic outbreak.

Ms. Gabriela Narváez from the Genetics Department with Paolo the alpaca

Ms. Gabriela Narváez from the Genetics Department with Paolo the alpaca
The alpaca Buddha who has created numerous nanobodies to the SARS-CoV-2 virus

The alpaca Buddha who has created numerous nanobodies to the SARS-CoV-2 virus
The alpaca Danny is part of a collaborative grant with the Max Planck Institute, Munich, Germany.

The alpaca Danny is part of a collaborative grant with the Max Planck Institute, Munich, Germany.
From left: Buddha, the alpaca who generated nanobodies to SARS-CoV-2, along with the alpacas Dario, Sergio, and Alex. Dario has been successful in creating nanobodies to the Ebola virus.

From left: Buddha, the alpaca who generated nanobodies to SARS-CoV-2, along with the alpacas Dario, Sergio, and Alex. Dario has been successful in creating nanobodies to the Ebola virus.

Follow the Alpacas

Nineteen alpacas live at the University of Austral where they are lovingly cared for by scientists and veterinarians. Buddha is the name of the alpaca who has generated several different neutralizing antibodies to SARS-CoV-2. Pedro the alpaca has been working to fight Nipah virus. The alpacas Seba and Martin are working to produce nanobodies against Hanta virus and the alpaca Dario creates nanobodies against Ebola virus.

Their contribution to fighting global pandemics are a yearly vaccination and subsequent, small blood draws. Mostly, their lives consist of sleeping, eating, and roaming their pastures.

If you’re interested in keeping up to date with these virus-fighting alpacas, you can join their almost 17,000 social media followers on Instagram.

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