Abstract
Abstract Background Recombinant Modified Vaccinia virus Ankara (MVA) is a replication-deficient viral vector platform with a favorable safety profile that is currently developed for multiple indications, including vaccines against emerging infections. We assessed the safety and immunogenicity of two MVA-based vaccine candidates against COVID-19 encoding the native or pre-fusion stabilized SARS-CoV-2 spike antigen, namely MVA-SARS-2-S and MVA-SARS-2-ST, in two clinical Phase I trials. Methods We conducted a first-in-human trial of the vaccine candidate MVA-SARS-2-S (NCT04569383) and a Phase Ib trial of the successor vaccine MVA-SARS-2-ST (NCT05226390) in healthy, SARS-CoV-2 immune-naïve adults aged between 18-55 (MVA-SARS-2-S) and 18-64 (MVA-SARS-2-ST) years. MVA-SARS-2-S expresses the native, full-length spike glycoprotein of SARS-CoV-2 (S), while MVA-SARS-2-ST delivers a pre-fusion stabilized spike antigen (ST). Both trials were designed as open-label dose-escalation trials and vaccinations were administered as a prime-boost regimen on days 0 and 28. Detailed safety and immunogenicity assessments were conducted at multiple timepoints throughout the study until day 168. Results In NCT04569383, 30 individuals received either 1 x 107 ± 0.5 log IU (IU=International Units, n=15, lower dose) or 1 x 108 ± 0.5 log IU (n=15, higher dose) of MVA-SARS-2-S. In NCT05226390, 8 participants received a lower (≥ 1 x 107 IU) and 7 participants a higher (≥ 5 x 107 IU) dose of MVA-SARS-2-ST. Both vaccines were well-tolerated and no vaccine-related severe adverse events (SAEs) occurred in either trial. However, seroconversion rates, measured as binding anti-SARS-CoV-2 S1 antibodies, could only be observed in 3/15 participants in the high dose cohort and none in the low dose cohort after vaccination with MVA-SARS-2-S. In contrast, all participants who received MVA-SARS-2-ST (n=15) achieved seroconversion independent of administered dose. Conclusion Both vaccine candidates were safe and well-tolerated. While MVA-SARS-2-S did not induce adequate immunogenicity, vaccination with the pre-fusion stabilized successor vaccine MVA-SARS-2-ST induced seroconversion in all vaccinees, demonstrating the significance of SARS-CoV-2 spike antigen conformation for vaccine immunogenicity. Disclosures Anahita Fathi, MD, Biotest: Honoraria Sibylle C. Mellinghoff, MD, Gilead: Grant|Octapharma: Advisor/Consultant
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