Immunogenicity of Synthetic MVA-based Vaccine COH04S1 Against SARS-CoV-2 in Post-HCT/CAR-T Patients and Its Cross-Protective Potential Against Mpox 9352
Year: 2025
Type: article
Abstract: Description Hematopoietic cell transplantation (HCT) and CAR-T cell therapy patients face increased risks from SARS-CoV-2 due to immunosuppression and limited vaccine responsiveness. In a phase 2 trial of hematologic malignancy (HM) patients post-HCT/CAR-T, we assessed the immunogenicity of the MVA-(modified vaccinia Ankara) based COVID-19 vaccine COH04S1 (licensed as GEO-CM04S1 by GeoVax, Inc.), which co-expresses spike (S) and nucleocapsid (N) antigens. Thirteen patients vaccinated 3–12 months post-HCT/CAR-T with 2–4 doses of COH04S1 displayed robust S- and N-specific humoral and cellular responses, including cross-neutralizing antibodies effective against variants of concern such as Omicron XBB.1.5. T-cell responses, predominantly CD4+, remained elevated at six months post-vaccination. Immune responses in HCT/CAR-T patients were superior or comparable to those in healthy volunteers (HV) and healthcare workers (HCW) vaccinated with Comirnaty®. Parallel studies revealed COH04S1’s potential cross-protection against MPXV (monkeypox virus). In human volunteers and non-human primates (NHPs), COH04S1 elicited orthopoxvirus-specific and MPXV cross-reactive immune responses, including MPXV cross-neutralizing antibodies comparable to JYNNEOS. In mpox-susceptible mice, COH04S1 and its sMVA backbone protected against lung infection following MPXV challenge. These findings highlight COH04S1’s dual potential as a SARS-CoV-2 vaccine for immunocompromised patients and cross-protection against mpox. Funding Sources Funding was provided by the Carol Moss Foundation, donors Julie and Roger Baskes, Judd Malkin and Michael Zweig. Topic Categories Vaccines and Immunotherapy (VAC)
Source: The Journal of Immunology
Authors: Sandra Ortega-Francisco, Sandra Ortega-Francisco, Flavia Chiuppesi, Miguel-Angel Gutierrez, Jing Li, Jada Mack-Onyeike, Corina La Rosa, Qiao Zhou, Jennifer Drake, Cynthia Slape, Paul Frankel, Teodora Kaltcheva, Angela Patterson, Shannon Dempsey, Felix Wussow, John Zaia, Randy Taplitz Taplitz, Sanjeet Dadwal Dadwal, Kelly McKee, Erica Raiden, Don Diamond
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4416450778
FWCI:
Cites:
Cited by:
Related to: