| Autor: |
Viviane M. Andrade, Kathleen Cashman, Kyle Rosenke, Eric Wilkinson, Nicole Josleyn, Ginger Lynn, Jesse Steffens, Sean Vantongeren, Jay Wells, Connie Schmaljohn, Paul Facemire, Jingjing Jiang, Jean Boyer, Aditya Patel, Friederike Feldmann, Patrick Hanley, Jamie Lovaglio, Kimberly White, Heinz Feldmann, Stephanie Ramos, Kate E. Broderick, Laurent M. Humeau, Trevor R. F. Smith |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Communications Medicine, Vol 4, Iss 1, Pp 1-14 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2730-664X |
| DOI: |
10.1038/s43856-024-00684-8 |
| Popis: |
Abstract Background We have previously developed a DNA-based vaccine, INO-4500, encoding the Lassa lineage IV glycoprotein precursor. INO-4500, when delivered with electroporation, elicited humoral and cellular responses, and conferred 100% protection in cynomolgus non-human primates. Here, we expanded the characterization of INO-4500 assessing immunogenicity and protective efficacy of lower doses and single immunization, and the durability of immune responses. Methods The study was divided into three arms evaluating INO-4500 vaccination: Arm 1 – Dosing regimen; Arm 2 – Single immunization; and Arm 3—Durability of immune responses and protective efficacy. Humoral and T cell responses were assessed by IgG binding ELISA, IFNγ ELISpot and flow cytometry-based T cell activation assays. NHPs were challenged with a lethal dose of Lassa lineage IV 8 weeks (Arms 1 and 2) or one year (Arm 3) after immunization. NHPs were assigned clinical scores and monitored for survival. Viremia, virus neutralization and release of soluble mediators were assessed post-challenge, as well as disease pathology following NHPs death or euthanasia. Results INO-4500 induces dose-dependent immune responses and protective efficacy. Animals receiving two doses of 2 mg of INO-4500 show complete short- and long-term LASV protection. NHPs receiving 1 mg of INO-4500 are protected from LASV challenge one year after vaccination but are only partially protected 8 weeks post-vaccination. LASV-specific memory T cells are present in vaccinated NHPs one year after vaccination. INO-4500 vaccination prevents NHPs from developing severe disease. Conclusions These studies demonstrate that INO-4500 can provide short- and long-term protection in NHPs from lethal LASV challenge. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
Full text from SpringerLink