As SARS-CoV-2 has evolved and mutated, therapeutic antibodies that worked early in the pandemic have become less effective, and newer variants, especially omicron, have developed ways to evade the antibodies we make in response to vaccines. A new, broadly neutralizing antibody developed at Boston Children's Hospital could potentially improve our ability to defend against future variants. In tests, it neutralized all currently known SARS-CoV-2 variants of concern, including all omicron variants. 

"We hope that this humanized antibody will prove to be as effective at neutralizing SARS-CoV-2 in patients as it has proven to be thus far in preclinical evaluations," says Frederick Alt, Ph.D., of the Program in Cellular and Molecular Medicine at Boston Children's Hospital, who co-led the research. 

As described in Science Immunology on August 11, Alt and Sai Luo, Ph.D., in his lab turned to a modified version of a humanized mouse model that the lab has used to search for broadly neutralizing antibodies to HIV, another virus that frequently mutates. The mice essentially have built-in human immune systems, and the model mimics the trial-and-error process our immune system uses to create increasingly effective antibodies.

The researchers first inserted two human gene segments into the mice, pushing their B cells to rapidly produce a diverse repertoire of humanized antibodies. They then exposed the mice to the SARS-CoV-2 spike protein, the main protein targeted by our antibodies and current vaccines, from the original Wuhan-Hu-1 strain of the virus. In response, the modified mice produced nine lineages or "families" of humanized antibodies that bound to the spike.