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

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)