Gene Transfer of ZMapp Antibodies Mediated by Recombinant Adeno-Associated Virus Protects Against Ebola Infections

Marc André Robert, Nasha Nassoury, Parminder S. Chahal, Marie Hélène Venne, Trina Racine, Xiangguo Qiu, Gary Kobinger, Amine Kamen, Rénald Gilbert, Bruno Gaillet

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Vectored delivery of the ZMapp antibody cocktail (c2G4, c4G7, and c13C6) by using recombinant adeno-associated viruses (rAAVs) could be useful for preventive immunization against Ebola virus infections because rAAVs can generate long-term antibody expression. Three rAAVs (serotype 9) encoding chimeric ZMapp antibodies were produced by triple-plasmid transfection up to 10 L-scale in WAVE bioreactors using HEK293 cells grown in suspension/serum-free conditions. Efficacy of AAV-c2G4 via intravenous (i.v.), intramuscular (i.m.), and intranasal (i.n.) routes of administration was evaluated in mice with two different doses of 2.7 × 10 10 and 13.0 × 10 10 vector genomes (vg). The best protective efficacies after Ebola challenge were obtained with the i.v. and i.m. routes. Serum concentrations of ZMapp antibodies positively correlated with survivability. Efficacy of the rAAV-ZMapp cocktail was then evaluated at a higher dose of 30.0 × 10 10 vg. It conferred a more robust protection (90% i.v. and 60% i.m.) than rAAV-c4G7 (30%) and rAAV-c13C6 (70%), both administered separately at the same dose. Delivery of rAAV-c2G4 alone achieved up to 100% protection (100% i.v. and 90% i.m.) at the same dose. In conclusion, the preventive treatment was effective in mice. However, no advantage was observed for using the rAAV-ZMapp cocktail in comparison to the utilization of the single rAAV-c2G4.

Original languageEnglish (US)
Pages (from-to)452-466
Number of pages15
JournalHuman Gene Therapy
Volume29
Issue number4
DOIs
StatePublished - Apr 2018
Externally publishedYes

Keywords

  • AAV
  • AAV manufacturing
  • antibody gene transfer
  • Ebola virus
  • humoral response
  • mouse
  • preventive treatment
  • ZMapp

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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