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Cited by 6Virus-based gene therapy researchInfluenza Virus Research StudiesRNA Interference and Gene Delivery

Integrase-Defective Lentiviral Vectors for Delivery of Monoclonal Antibodies against Influenza

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Michelini, Zuleika, Minkoff, Judith M., Yang, Jianjun, Negri, Donatella, Cara, Andrea, Hanson, Brendon J., Salvatore, Mirella·2020·Viruses
DOI 10.3390/v12121460PMC PMC7767071
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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.

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  • In an in vivo study involving H5 influenza A virus, monoclonal antibody administered through NILVs did not persist for longer time points.

    “On the other hand, one in vivo study involving the H5 influenza A virus (IAV) demonstrated that the monoclonal antibody (mAb) administered through NILVs did not persist for longer time points [80].”

    From Non-Integrating Lentiviral Vectors in Clinical Applications: A Glance Through (2022) · cites this paper as [80]

    Results §3.4 reports that protection against H5N1 challenge was lost when mice were challenged 30 days after IDLV administration. It does not establish that the antibody itself failed to persist: Results §3.3 detected the antibody through day 28, and §3.4 offers reduced antibody levels at day 30 only as a possible explanation for the loss of protection. (LLM, conf=0.87)

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Cited by

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Authors
Michelini, Z., Minkoff, J. M., Yang, J., Negri, D., Cara, A., Hanson, B. J., & Salvatore, M.
Affiliations
  • Weill Cornell Medicine (US)
  • Istituto Superiore di Sanità (IT)
  • DSO National Laboratories (SG)
Corresponding author
Salvatore, Mirella
ORCID
Venue
Viruses
Publisher
MDPI AG
Published
2020-12-17
Volume
12
Issue
12
Pages
1460
ISSN
1999-4915 (ISSN-L)
DOI
10.3390/v12121460
PMC
PMC7767071
OpenAlex
W3112080665
Cited by
6
References
4
Citations by year
2026: 1 · 2025: 1 · 2023: 1 · 2022: 3
FWCI
0.59
Type
journal article
Language
en
Open access
Licence
Locations
  • Viruses (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institutes of Health (1R21AI124141-01)
  • National Center for Advancing Translational Sciences (UL1TR002384)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
  • Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Keywords
integrase-defective lentiviral vectors, monoclonal antibodies, influenza A virus, passive immunotherapy, hemagglutinin, intranasal administration, intramuscular administration, non-integrating vectors
MeSH terms
Animals, Antibodies, Monoclonal, Antibodies, Viral, Enzyme-Linked Immunosorbent Assay, Female, Genetic Vectors, Humans, Orthomyxoviridae Infections, Influenza A virus, Gene Expression, Lentivirus, Gene Transfer Techniques, Hemagglutinin Glycoproteins, Influenza Virus, HIV Integrase, Gene Order, Mice, HEK293 Cells

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