COVID: How one person’s cells led to our only antibody treatment for omicron

Years ago, a survivor of a previous deadly pandemic gave a gift that is helping save desperately ill COVID-19 patients today.

The donation – a blood sample holding infection-fighting cells from the deadly 2003 SARS outbreak – is the basis of a new Bay Area-designed therapy that is now the sole monoclonal antibody that can fend off the omicron variant, preventing serious illness or death, as traditional treatments fail.

“Currently it’s the only monoclonal therapy that works,” said Dr. Warner Greene, director of Gladstone Institute of Virology and Immunology at UC San Francisco.

Called sotrovimab, the treatment is so precious that hospitals are running out. As COVID-19 cases soar, the federal government has contracted for 600,000 doses from San Francisco-based company Vir Biotechnology, boosting the young company’s estimated 2022 revenues to a stunning $2 billion, according to Cowen Equity Research.

“It’s a great achievement. It’s an important tool for patients at high risk of getting worse, or being hospitalized,” said infectious disease specialist Dr. Daniel Shin of El Camino Hospital in Mountain View. “Demand is outpacing the supply.”

Monoclonal antibodies have been a mainstay of COVID-19 treatment since the early days of the current pandemic, earning testimonials from former President Donald Trump, former New Jersey Gov. Chris Christie, attorney Rudy Giuliani and thousands of other high-risk Americans.

They boost the body’s ability to fight off the virus, helping patients with weakened immune systems whose own antibodies aren’t enough to protect them.

Early on in the pandemic, the federal government bet big on two monoclonal antibody manufacturers — Regeneron and Eli Lilly — signing hefty contracts to boost production. Those treatments saved thousands of lives.

But when omicron emerged, that medicine cabinet was suddenly useless. The Eli Lilly and Regeneron products are based on antibodies from survivors of the current pandemic. But they didn’t anticipate future variants’ ability to evade immunity, and ended up making a crucial design mistake: They targeted the treatment on a part of the pathogen that changes.

Vir, headquartered in Mission Bay, embraced a very different approach. It proved prescient.

Its scientists asked: Would the antibodies of people who successfully fought off China’s 2003 SARS CoV-1 virus also protect against SARS CoV-2 – the virus causing our current coronavirus misery? The viruses are cousins and cause similar flu-like illnesses.

Any antibody that works against both viruses must target a place on the pathogen that’s common to both — a region so essential to viral survival that it’s unchanged by evolution, they reasoned. The newly emerged omicron, despite its dazzling 36 mutations, might be equally vulnerable.

“If an antibody inhibits those two different viruses, it is more likely to inhibit variants as they arise,” said Vir CEO George Scangos. “We thought: ‘Let’s not chase our tail. Let’s get ahead of the virus. Let’s develop an antibody that will retain its activity against variants.’ ”

The company holds a large library of blood samples from survivors of some of the world’s most frightening infections, such as Ebola, Zika and Dengue  – and SARS. Collected by subsidiary Humabs BioMed, the samples sleep in cold storage, frozen in liquid nitrogen tanks.

When the SARS outbreak receded, so did interest in the blood.

But that changed in December 2019. Alerted by news of a new pandemic, scientists at Vir jumped into action. They scanned the library, locating two SARS samples – one collected from an acutely ill patient in 2003 and the other from a recovered patient in 2013.

Blood was thawed, and antibodies were extracted. From a list of thousands, they narrowed it down to fewer than 15 antibodies.

In thrilling lab experiments, Vir watched the antibodies subdue the new virus. But how did they work? Which were best? For answers, they needed to see molecular structures and behaviors, so they turned to Lawrence Berkeley National Laboratory.

Like just about everywhere in April 2020, the lab was closed. The Bay Area was under a strict shelter-in-place order.

“We went to the managers and said, ‘We have SARS samples. Please let us do the work,’ ” recalled Jay Nix, leader of the lab’s Molecular Biology Consortium. “They didn’t blink an eye,” and unlocked the doors.

Small trays of crystalized antibodies and virus, carefully packed in Styrofoam, were driven to Berkeley. There, in the lab’s empty parking lot, Nix met Vir protein chemist Nadine Czudnochowski for a handoff.

Using a technique called X-ray crystallography, Nix witnessed how the antibodies latched onto a specific spot on the surface of the virus, blocking infection. He generated 3D structural maps of this interaction, helping Vir select the most promising contenders and advance them to animal, and later human, trials.

“We were able to understand how these things work, at the atomic level,” Nix said.

Vir picked one antibody – S309 – for manufacturing. In the blood sample, they identified the B-cells that make S309, harvested them and nudged them to replicate, creating a large cloned cluster of cells. Then they improved upon Mother Nature, enlisting teams in San Francisco and Switzerland, collaborating with pharmaceutical giant GlaxoSmithKline. Using specialized techniques, they engineered changes to S309 to help fortify the immune response.

“It grabs the Achilles’ heel of the virus,” said Jeremy Kamil, a virologist at Louisiana State University Health Sciences Center Shreveport, who studies variant mutations.

“Vir’s strategic expertise, and the elegance of their approach, rewarded them,” he said. “That paid dividends.”

The result would be called sotrovimab, which neutralizes all known SARS-CoV-2 strains, including mutants. It is infused into patients over an hour, so must be taken in a hospital or clinic, within 10 days of symptoms. Scientists hope to develop a quick intramuscular injection.