TY - JOUR
T1 - Safety, tolerability, and immunogenicity of INO-4500, a synthetic DNA-based vaccine against Lassa virus, in a phase 1b clinical trial in healthy Ghanaian adults
AU - Koram, Kwadwo Ansah
AU - Walker, Kathleen A.
AU - Orizu, Bonaventure
AU - Marrero, Idania
AU - Boyer, Jean
AU - Yang, Shu Ping
AU - Broderick, Kate E.
AU - Kusi, Kwadwo Asamoah
AU - Kyei-Baafour, Eric
AU - Ofori, Ebenezer Addo
AU - Pobee, Abigail
AU - Adu-Amankwah, Susan
AU - Amoakoh-Coleman, Mary
AU - Amoakoh, Hannah Brown
AU - Abuaku, Benjamin
AU - Badji, Edem
AU - Ntiri, Michael
AU - Quaye, Lydia
AU - Morrow, Matthew P.
AU - Sylvester, Albert J.
AU - Reuschel, Emma L.
AU - Gillespie, Elisabeth
AU - Liebowitz, David
AU - Humeau, Laurent M.
N1 - Publisher Copyright:
Copyright © 2025 Koram, Walker, Orizu, Marrero, Boyer, Yang, Broderick, Kusi, Kyei-Baafour, Ofori, Pobee, Adu-Amankwah, Amoakoh-Coleman, Amoakoh, Abuaku, Badji, Ntiri, Quaye, Morrow, Sylvester, Reuschel, Gillespie, Liebowitz and Humeau.
PY - 2025/10/24
Y1 - 2025/10/24
N2 - 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,
AB - 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,
KW - DNA medicine
KW - electroporation (EP)
KW - immunogenicity
KW - Lassa fever
KW - Lassa virus (LASV)
KW - safety
KW - vaccine
UR - https://www.scopus.com/pages/publications/105021200475
U2 - 10.3389/fimmu.2025.1658549
DO - 10.3389/fimmu.2025.1658549
M3 - Article
C2 - 41208990
AN - SCOPUS:105021200475
SN - 1664-3224
VL - 16
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 1658549
ER -