NIH-funded team develops method to identify future SARS-CoV-2 mutations that could affect rapid antigen test performance
A research team funded by the National Institutes of Health has shown that commercially available rapid antigen tests can detect past and present variants of concern and has identified potential mutations that may impact test performance in the future.
The team, which was funded by NIH’s Rapid Acceleration of Diagnostics (RADx) Tech program, developed a method to evaluate how mutations to SARS-CoV-2 can affect recognition by antibodies used in rapid antigen tests. Since most rapid antigen tests detect the SARS-CoV-2 nucleocapsid protein, or N protein, the team directly measured how mutations to the N protein impacted diagnostic antibodies’ ability to recognize their target.
The study, published in Cell, used a method called deep mutational scanning to simultaneously evaluate how any single amino acid substitution in the N protein could affect diagnostic antibody binding. The researchers generated an exhaustive library of N protein variations, which includes nearly 8,000 single amino acid substitutions – representing more than 99.5% of all possible mutations – and evaluated their interaction with 17 different diagnostic antibodies used in 11 commercially available rapid antigen tests. Rapid antigen tests often employ two different diagnostic antibodies for the detection of the SARS-CoV-2 virus.
For each diagnostic antibody evaluated, the researchers documented which mutations to the N protein affected antibody recognition. From this information, they created an ‘escape mutation profile’ for each antibody, which lists the specific mutations to the N protein that have an effect on the antibody’s ability to bind to its target. While several diagnostic antibodies recognized the same region of the N protein, the researchers found that each antibody had a unique escape mutation profile. As the SARS-CoV-2 virus continues to develop mutations, this data can be used to flag specific antibodies whose diagnostic performance may need to be reassessed.
