The DNA-based Lassa vaccine INO-4500 confers durable protective efficacy in cynomolgus macaques against lethal Lassa fever
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 expan...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-11-01
|
| Series: | Communications Medicine |
| Online Access: | https://doi.org/10.1038/s43856-024-00684-8 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850064838001164288 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Viviane M. Andrade |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-db3fb6d49d26402a8130cf02b1e9ffb8 |
| institution | DOAJ |
| issn | 2730-664X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Medicine |
| spelling | doaj-art-db3fb6d49d26402a8130cf02b1e9ffb82025-08-20T02:49:09ZengNature PortfolioCommunications Medicine2730-664X2024-11-014111410.1038/s43856-024-00684-8The DNA-based Lassa vaccine INO-4500 confers durable protective efficacy in cynomolgus macaques against lethal Lassa feverViviane M. Andrade0Kathleen Cashman1Kyle Rosenke2Eric Wilkinson3Nicole Josleyn4Ginger Lynn5Jesse Steffens6Sean Vantongeren7Jay Wells8Connie Schmaljohn9Paul Facemire10Jingjing Jiang11Jean Boyer12Aditya Patel13Friederike Feldmann14Patrick Hanley15Jamie Lovaglio16Kimberly White17Heinz Feldmann18Stephanie Ramos19Kate E. Broderick20Laurent M. Humeau21Trevor R. F. Smith22Inovio Pharmaceuticals Inc.Virology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID)Laboratory of Virology (LV), Division of Intramural Research (DIR), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Rocky Mountain Laboratories (RML)Virology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID)Virology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID)Virology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID)Virology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID)Virology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID)Virology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID)Office of the Chief Scientists, Headquarters, United States Army Medical Research Institute of Infectious DiseasesPathology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID)Inovio Pharmaceuticals Inc.Inovio Pharmaceuticals Inc.Inovio Pharmaceuticals Inc.Rocky Mountain Laboratory Veterinary Branch (RMVB), Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Rocky Mountain Laboratories (RML)Rocky Mountain Laboratory Veterinary Branch (RMVB), Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Rocky Mountain Laboratories (RML)Rocky Mountain Laboratory Veterinary Branch (RMVB), Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Rocky Mountain Laboratories (RML)Laboratory of Virology (LV), Division of Intramural Research (DIR), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Rocky Mountain Laboratories (RML)Laboratory of Virology (LV), Division of Intramural Research (DIR), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Rocky Mountain Laboratories (RML)Inovio Pharmaceuticals Inc.Inovio Pharmaceuticals Inc.Inovio Pharmaceuticals Inc.Inovio Pharmaceuticals Inc.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.https://doi.org/10.1038/s43856-024-00684-8 |
| spellingShingle | 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 The DNA-based Lassa vaccine INO-4500 confers durable protective efficacy in cynomolgus macaques against lethal Lassa fever Communications Medicine |
| title | The DNA-based Lassa vaccine INO-4500 confers durable protective efficacy in cynomolgus macaques against lethal Lassa fever |
| title_full | The DNA-based Lassa vaccine INO-4500 confers durable protective efficacy in cynomolgus macaques against lethal Lassa fever |
| title_fullStr | The DNA-based Lassa vaccine INO-4500 confers durable protective efficacy in cynomolgus macaques against lethal Lassa fever |
| title_full_unstemmed | The DNA-based Lassa vaccine INO-4500 confers durable protective efficacy in cynomolgus macaques against lethal Lassa fever |
| title_short | The DNA-based Lassa vaccine INO-4500 confers durable protective efficacy in cynomolgus macaques against lethal Lassa fever |
| title_sort | dna based lassa vaccine ino 4500 confers durable protective efficacy in cynomolgus macaques against lethal lassa fever |
| url | https://doi.org/10.1038/s43856-024-00684-8 |
| work_keys_str_mv | AT vivianemandrade thednabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT kathleencashman thednabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT kylerosenke thednabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT ericwilkinson thednabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT nicolejosleyn thednabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT gingerlynn thednabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT jessesteffens thednabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT seanvantongeren thednabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT jaywells thednabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT connieschmaljohn thednabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT paulfacemire thednabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT jingjingjiang thednabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT jeanboyer thednabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT adityapatel thednabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT friederikefeldmann thednabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT patrickhanley thednabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT jamielovaglio thednabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT kimberlywhite thednabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT heinzfeldmann thednabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT stephanieramos thednabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT kateebroderick thednabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT laurentmhumeau thednabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT trevorrfsmith thednabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT vivianemandrade dnabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT kathleencashman dnabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT kylerosenke dnabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT ericwilkinson dnabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT nicolejosleyn dnabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT gingerlynn dnabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT jessesteffens dnabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT seanvantongeren dnabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT jaywells dnabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT connieschmaljohn dnabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT paulfacemire dnabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT jingjingjiang dnabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT jeanboyer dnabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT adityapatel dnabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT friederikefeldmann dnabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT patrickhanley dnabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT jamielovaglio dnabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT kimberlywhite dnabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT heinzfeldmann dnabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT stephanieramos dnabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT kateebroderick dnabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT laurentmhumeau dnabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever AT trevorrfsmith dnabasedlassavaccineino4500confersdurableprotectiveefficacyincynomolgusmacaquesagainstlethallassafever |