Tweet
Proc Natl Acad Sci U S A
. 2023 Jun 6;120(23):e2303509120.
doi: 10.1073/pnas.2303509120. Epub 2023 May 30. Vectored immunoprophylaxis and treatment of SARS-CoV-2 infection in a preclinical model
Takuya Tada 1 , Julia Minnee 1 , Nathaniel R Landau 1
Affiliations
Vectored immunoprophylaxis was first developed as a means of establishing engineered immunity to HIV using an adenoassociated viral vector expressing a broadly neutralizing antibody. We applied this concept to establish long-term prophylaxis against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a mouse model using adenoassociated virus and lentiviral vectors expressing a high-affinity angiotensin-converting enzyme 2 (ACE2) decoy. Administration of decoy-expressing (adenoassociated virus) AAV2.retro and AAV6.2 vectors by intranasal instillation or intramuscular injection protected mice against high-titered SARS-CoV-2 infection. AAV and lentiviral vectored immunoprophylaxis was durable and was active against SARS-CoV-2 Omicron subvariants. The AAV vectors were also effective therapeutically when administered postinfection. Vectored immunoprophylaxis could be of value for immunocompromised individuals for whom vaccination is not practical and as a means to rapidly establish protection from infection. Unlike monoclonal antibody therapy, the approach is expected to remain active despite continued evolution viral variants.
Keywords: AAV vector; ACE2 decoy; SARS-CoV-2; immunoprophylaxis; lentiviral vector.
. 2023 Jun 6;120(23):e2303509120.
doi: 10.1073/pnas.2303509120. Epub 2023 May 30. Vectored immunoprophylaxis and treatment of SARS-CoV-2 infection in a preclinical model
Takuya Tada 1 , Julia Minnee 1 , Nathaniel R Landau 1
Affiliations
- PMID: 37252952
- DOI: 10.1073/pnas.2303509120
Vectored immunoprophylaxis was first developed as a means of establishing engineered immunity to HIV using an adenoassociated viral vector expressing a broadly neutralizing antibody. We applied this concept to establish long-term prophylaxis against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a mouse model using adenoassociated virus and lentiviral vectors expressing a high-affinity angiotensin-converting enzyme 2 (ACE2) decoy. Administration of decoy-expressing (adenoassociated virus) AAV2.retro and AAV6.2 vectors by intranasal instillation or intramuscular injection protected mice against high-titered SARS-CoV-2 infection. AAV and lentiviral vectored immunoprophylaxis was durable and was active against SARS-CoV-2 Omicron subvariants. The AAV vectors were also effective therapeutically when administered postinfection. Vectored immunoprophylaxis could be of value for immunocompromised individuals for whom vaccination is not practical and as a means to rapidly establish protection from infection. Unlike monoclonal antibody therapy, the approach is expected to remain active despite continued evolution viral variants.
Keywords: AAV vector; ACE2 decoy; SARS-CoV-2; immunoprophylaxis; lentiviral vector.