SARS-CoV-2, the virus that causes COVID-19, has mutated many times into new variants, some that we don't hear about because they haven't changed the course of the pandemic, while others have become variants of concern, and spread widely. Some of the genetic mutations have enabled the virus to evade the immune system in new ways, a major concern with one of the latest variants, Omicron. But scientists have now identified some powerful antibodies that can take down many different variants of SARS-CoV-2. Two unrelated studies have been reported in Science Immunology and Science Translational Medicine, which have described these antibodies.
The first study used a mouse model that has been genetically modified to carry an immune system that mimics ours. The humanized mice carry two human gene segments that drive B cells to produce various humanized antibodies. When exposed to a virus, the immune systems of these mice will generate antibodies that fight the pathogen, just like human immune systems.
Researchers used this approach, exposing the mice to SARS-CoV-2, and analyzing the many antibodies that were generated. The scientists were able to isolate an antibody, called SP1-77 that neutralized every variant of concern of SARS-CoV that we currently know of, including different strains of Omicron. Other members of the SP1-77 lineage were also effective. The findings have been reported in Science Immunology.
"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," said study co-leader Frederick Alt, PhD, of Boston Children's Hospital.
A structural assessment suggested that the SP1-77 antibody can bind to a crucial portion of the SARS-CoV-2 spike protein called the receptor-binding domain (RBD), which enables the virus to enter cells. But, the antibody doesn't bind to the portion of the RBD that makes direct contact with a host cell's ACE2 receptor, the viral entry point. This makes this antibody very different from those that are currently used, and it binds to a part of SARS-CoV-2 that has not mutated yet.
In a different study reported in Science Translational Medicine, researchers used a rhesus macaque model because some animals are known to be better at producing antibodies that can fight SARS-type viruses. The macaques were exposed to SARS-CoV-2, and these animals generated antibodies that are able to neutralize the virus in a broad way - many variants can be targeted. The macaque genome is slightly different from the human genome, making their immune response is more broad, while the human response sacrifices that broadness for potency.
The scientists noted that the macaque antibodies are targeting a portion of the spike protein that is not typically mutated. Like the other study, this research has stressed the effectiveness of antibodies that target other regions of the virus or the RBD while avoiding the portion of the spike protein that binds directly to the ACE2 receptor. The antibodies described in this research bind to the edge of the ACE2 binding site.
Both studies have noted that these findings could inform vaccine research. Scientists may be able to use the structural data derived from the research to create vaccines that will work against many types of SARS-CoV-2, both known and unknown.
Sources: Children's Hospital Boston, Scripps Research Institute, Science Immunology, Science Translational Medicine
