Safety, Tolerability, and Immunogenicity of INO-4500, a Synthetic DNA-based Vaccine against Lassa Virus (LASV), in a Phase 1b Clinical Trial in Healthy Ghanaian Adults

Kwadwo Ansah Koram¹Kathleen A Walker²Bonaventure Orizu²Idania Marrero²Jean Boyer²ShuPing Yang²Kate E Broderick²Kwadwo Asamoah Kusi³Eric Kyei-Baafour³EBENEZER ADDO OFORI³Abigail Pobee³Susan Adu-Amankwah¹Mary Amoakoh Coleman¹Hannah Brown Amoakoh^1,4Benjamin Abuaku¹Edem Badji¹Michael Ntiri¹Lydia Quaye¹Matthew P Morrow²Albert J Sylvester²Emma L Reuschel²Elisabeth Gillespie²David Liebowitz²Laurent M Humeau^2*

• ¹Department of Epidemiology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon-Accra, Ghana
• ²Inovio Pharmaceuticals Inc, Plymouth Meeting, United States
• ³Department of Immunology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon-Accra, Ghana
• ⁴Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht University, Utrecht, Netherlands

Background Lassa fever (LF) is an acute viral hemorrhagic illness endemic to West Africa, with no licensed vaccines or targeted treatments available, highlighting a critical gap in global health preparedness. T cell-mediated immunity plays a central role in viral control and survival. Synthetic DNA vaccines offer a promising strategy to induce both humoral and cellular immunity against LF. Methods A Phase 1b, randomized, double-blind, placebo-controlled trial was conducted to assess the safety, tolerability, and immunogenicity of INO-4500, a DNA vaccine encoding the Lassa virus (Josiah strain) glycoprotein precursor (GPC). A total of 220 healthy adults were randomized to receive either 1 mg or 2 mg of INO-4500 (intervention), or placebo, administered intradermally (ID) followed by electroporation (EP) at Day 0 and Week 4. Safety was evaluated through Week 48. Primary immunogenicity endpoints included humoral and cellular immune responses at multiple timepoints post-vaccination. Results INO-4500 was well tolerated, with no Grade 3 or higher treatment-emergent adverse events (TEAEs) deemed to be related to the intervention; 88.6% of all TEAEs were Grade 1. No cases of attributable hearing loss were reported. INO-4500 groups demonstrated statistically significant increases in Lassa virus GPC-specific binding antibodies at Weeks 6 and 12 compared to placebo, with the 2 mg group eliciting the strongest responses. T cell responses remained elevated above baseline through Week 48 in both INO-4500 groups, indicating durable cellular immunity. Conclusions DNA vaccine INO-4500 was well tolerated and elicited durable humoral and cellular immune responses in healthy adults. These findings support further clinical development of INO-4500 as a potential preventive vaccine to reduce LF-associated morbidity and mortality in endemic regions. Clinical trial registration: https://clinicaltrials.gov, identifier NCT04093076