Arming Antibodies Against COVID-19
SARS-CoV-2, the virus behind COVID-19, is powerful, tenacious even, and has spread quickly worldwide. But all viruses have weaknesses—and that’s what SickKids molecular scientist Dr. Jean-Philippe Julien aims to exploit.
Before COVID-19 emerged, the Julien lab was finding ways to neutralize infectious diseases like HIV/AIDS and malaria by harnessing the power of antibodies—proteins the body unleashes to fight infection.
Work halted abruptly in mid-March, when all but the most essential research at SickKids had to shut down and staff work from home. Labs scrambled to close, experiments were stopped and data lost.
“We ramped everything down in just one week,” says Dr. Julien. “But that weekend, we knew we had to contribute, the scale of COVID-19 was too catastrophic. We had the infrastructure, know-how, and expertise—and collaborators who’d already turned their attention to the virus.”
“It’s humbling. It’s a global moon shot.” ~Dr. JP Julien
Overnight, the lab switched gears. Like researchers around the globe, they are racing to understand how the virus replicates, where its weaknesses lie, and which antibodies are best able to neutralize it.
A virus must invade host cells in order to self-replicate. Most viruses have surface features—like SARS-CoV-2’s spikes—used to invade host cells. The Julien lab is hunting the antibodies best able to attack the spikes and prevent them from hooking onto the target.
They are also experimenting to find the most potent antibody combinations against SARS-CoV-2. Their approach draws on discoveries in the 1990s that HIV, one of the most highly mutating viruses, is stopped when attacked in at least three weak spots. Early studies of SARS-CoV-2 indicate that a multi-pronged attack will lay waste to it.
Discovery efforts screen thousands of antibodies before pinpointing the best. The challenge now is to quickly identify the most potent antibodies and the most effective combinations. Work that would normally take the lab years is being collapsed into months. A rapid response to COVID-19 means getting the most out of the first batch of candidate antibodies—carefully pre-selected with a biotech research partner.
The research team has another head start. Through their work on HIV/AIDS, Dr. Julien and collaborators have invented and patented a unique technology called Multabody for combining antibodies into a single-molecule drug.
“It’s part of the new arsenal against viruses that mutate highly and need to be hit broadly,” says Dr. Julien.
Once the most potent combination is discovered, the Julien lab will test it rigorously against SARS-CoV-2. If successful, their antibody-based therapy will be ready to manufacture and commercialized within months.
