Broadly neutralizing antibodies could fight novel COVID-19 variants

As the COVID-19 pandemic continues, new variants of the SARS-CoV-2 coronavirus have evolved ways to evade vaccines and the antibodies we make in response to previous infections. As a result, we’re seeing breakthrough cases where once-effective antibody treatments are becoming less effective over time. I have been looking for broadly neutralizing antibodies.

An antibody developed by researchers at Boston Children’s Hospital now appears to fit that bill. Neutralized the SARS-CoV-2 variant.

“We hope that this antibody will prove to be as effective in patients as it has been in previous preclinical evaluations.” Doctor.Frederick Alt of Cellular and Molecular Medicine Program at Boston Children, the principal investigator of the study. “If so, it may offer new treatments and contribute to new vaccine strategies as well.”

Create and test multiple antibodies

The team, led by Boston Children’s Dr. Alt and Dr. Sai Luo, first Mouse model created by Alt Labs to search for broadly neutralizing antibodies to HIV, another virus that mutates frequently. These mice essentially have a human immune system built-in. The modified model mimics and refines the trial-and-error process the immune system uses to create increasingly effective antibodies when it encounters an intruder.

Researchers first inserted two human gene segments into mice. This prompted their immune cells to rapidly produce a diverse repertoire of antibodies similar to those we might make ourselves. exposed to protein. This is the primary protein targeted by our antibodies and current vaccines from the original Wuhan-Hu-1 coronavirus strain.

In response, mice generated nine different ‘families’ of antibodies that bind spikes. Collaborator at Duke University, Ph.D. Alt and Luo then tested the efficacy of these antibodies.

Antibodies from 3 out of 9 families potently neutralized the original Wuhan-Hu-1 virus. However, one antibody family, specifically called SP1-77, showed broader activity neutralizing alpha, beta, gamma, delta, and all previous and current Omicron strains.

A new way to neutralize viruses

What makes SP1-77 so good at neutralizing viruses? Structural biology research by a collaborative team led by Dr. Bin Chen and Jun Chan of Boston Children Dr. Burton Haynes At Duke we showed that this antibody works in a unique way.

In order for SARS-CoV-2 to infect us, it must first attach to our cells’ ACE2 receptors. Much like the antibodies used to treat COVID-19, many of the antibodies we make in response to vaccines block this binding. They do so by binding to the spike’s receptor-binding domain (RBD) at specific locations. The SP1-77 antibody also binds to her RBD but does not otherwise prevent the virus from binding to her ACE2 receptor.

So how does it protect us? Once the virus binds to her ACE2, we need to complete the final step. That is, it fuses the outer membrane of the virus with the membrane of the cell. This opens the door to infection. Using a new live-cell imaging platform, Ph.D.with Alex Kreutzberger Thomas Kirchhausen You indicated that SP1-77 blocks this step.

“SP1-77 binds to the spike protein at a site not previously mutated in any variant and neutralizes these variants by a novel mechanism,” said Dr. Kirchhausen. “These properties may contribute to its broad and powerful activity.”

Better COVID-19 Vaccines and Treatments?

Researchers have applied for patents on both the antibodies and the mouse model used to make them. They want their work to develop commercially.

“It was an honor to work with this dedicated, collaborative team whose diverse expertise enabled us to uncover SP1-77,” says Alt. “We look forward to using our model to discover antibodies with therapeutic potential against other emerging pathogens.”

Survey results published of scientific immunology August 11th.