On Mar. 11, 2021, ImmunityBio announced it was developing a novel hAd5 ACE2 Decoy therapeutic vaccine to neutralize the SARS-CoV-2 virus, including the E484K and N501Y mutations. The company published the positive findings of high binding affinity to the variants in preprint server, bioRxiv entitled: A recombinant ACE2 triple decoy that traps and neutralizes SARS-CoV-2 shows enhanced affinity for highly transmissible SARS-CoV-2 variants.

The hAd5 ACE2 Decoy candidate is based on modified ACE2 receptors that would compete with ACE2 on the cells of respiratory tract for binding of the SARS-CoV-2 virus. The ACE2 Decoy would trap the virus, preventing it from infecting cells and facilitate clearance of the virus from the body.

ImmunityBio’s advanced molecular dynamic simulation capability previously reported in December was leveraged to design the ACE2 Decoy so it would have higher affinity for the virus, including SARS-CoV-2 variants, than natural ACE2 found on cells.

Given the recent emergence and rapid spread of COVID-19 cases due to several SARS-CoV-2 variants with mutations in the S RBD, including variants originating in the United Kingdom, South Africa and California, ImmunityBio scientists sought to identify a single ACE2 decoy candidate with robust binding affinity across wild-type and variant SARS-CoV-2 S RBDs, which might thus demonstrate efficacy in neutralizing infection with SARS-CoV-2 of any known genotype.

The ACE2 Decoy not only maintains its high affinity for S RBD expressing these mutations, but shows enhanced affinity for S RBD expressing the N501Y or L452R mutations and the highest affinity for S RBD expressing both the E484K and N501Y mutations. The candidate warrants continued development, beginning with testing in challenge studies.