tetano
Editor, Senior Moderator
Viruses
. 2020 Dec 17;12(12):E1460.
doi: 10.3390/v12121460.
Integrase-Defective Lentiviral Vectors for Delivery of Monoclonal Antibodies against Influenza
Zuleika Michelini[SUP] 1 [/SUP], Judith M Minkoff[SUP] 1 [/SUP], Jianjun Yang[SUP] 1 [/SUP], Donatella Negri[SUP] 2 [/SUP], Andrea Cara[SUP] 3 [/SUP], Brendon J Hanson[SUP] 4 [/SUP], Mirella Salvatore[SUP] 1 [/SUP]
Affiliations
Abstract
Delivering rapid protection against infectious agents to non-immune populations is a formidable public health challenge. Although passive immunotherapy is a fast and effective method of protection, large-scale production and administration of monoclonal antibodies (mAbs) is expensive and unpractical. Viral vector-mediated delivery of mAbs offers an attractive alternative to their direct injection. Integrase-defective lentiviral vectors (IDLV) are advantageous for this purpose due to the absence of pre-existing anti-vector immunity and the safety features of non-integration and non-replication. We engineered IDLV to produce the humanized mAb VN04-2 (IDLV-VN04-2), which is broadly neutralizing against H5 influenza A virus (IAV), and tested the vectors' ability to produce antibodies and protect from IAV in vivo. We found that IDLV-transduced cells produced functional VN04-2 mAbs in a time- and dose-dependent fashion. These mAbs specifically bind the hemagglutinin (HA), but not the nucleoprotein (NP) of IAV. VN04-2 mAbs were detected in the serum of mice at different times after intranasal (i.n.) or intramuscular (i.m.) administration of IDLV-VN04-2. Administration of IDLV-VN04-2 by the i.n. route provided rapid protection against lethal IAV challenge, although the protection did not persist at later time points. Our data suggest that administration of mAb-expressing IDLV may represent an effective strategy for rapid protection against infectious diseases.
Keywords: genetic immunization; influenza; integrase-defective lentiviral vector; monoclonal antibody; passive immunity.
. 2020 Dec 17;12(12):E1460.
doi: 10.3390/v12121460.
Integrase-Defective Lentiviral Vectors for Delivery of Monoclonal Antibodies against Influenza
Zuleika Michelini[SUP] 1 [/SUP], Judith M Minkoff[SUP] 1 [/SUP], Jianjun Yang[SUP] 1 [/SUP], Donatella Negri[SUP] 2 [/SUP], Andrea Cara[SUP] 3 [/SUP], Brendon J Hanson[SUP] 4 [/SUP], Mirella Salvatore[SUP] 1 [/SUP]
Affiliations
- PMID: 33348840
- DOI: 10.3390/v12121460
Abstract
Delivering rapid protection against infectious agents to non-immune populations is a formidable public health challenge. Although passive immunotherapy is a fast and effective method of protection, large-scale production and administration of monoclonal antibodies (mAbs) is expensive and unpractical. Viral vector-mediated delivery of mAbs offers an attractive alternative to their direct injection. Integrase-defective lentiviral vectors (IDLV) are advantageous for this purpose due to the absence of pre-existing anti-vector immunity and the safety features of non-integration and non-replication. We engineered IDLV to produce the humanized mAb VN04-2 (IDLV-VN04-2), which is broadly neutralizing against H5 influenza A virus (IAV), and tested the vectors' ability to produce antibodies and protect from IAV in vivo. We found that IDLV-transduced cells produced functional VN04-2 mAbs in a time- and dose-dependent fashion. These mAbs specifically bind the hemagglutinin (HA), but not the nucleoprotein (NP) of IAV. VN04-2 mAbs were detected in the serum of mice at different times after intranasal (i.n.) or intramuscular (i.m.) administration of IDLV-VN04-2. Administration of IDLV-VN04-2 by the i.n. route provided rapid protection against lethal IAV challenge, although the protection did not persist at later time points. Our data suggest that administration of mAb-expressing IDLV may represent an effective strategy for rapid protection against infectious diseases.
Keywords: genetic immunization; influenza; integrase-defective lentiviral vector; monoclonal antibody; passive immunity.