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Open Forum Infect Dis
. 2025 Nov 26;12(12):ofaf689.
doi: 10.1093/ofid/ofaf689. eCollection 2025 Dec. Phase 1 Randomized Controlled Trial of the Safety and Immunogenicity of the SARS-CoV-2 (Omicron BA.5) mRNA-CR-04 Vaccine in Adults 18-49 Years of Age
Abdi Naficy 1 , Mireille Venken 2 , Yingmei Xi 3 , Mark Loughrey 4 , Giulietta Maruggi 5 , Hema Sharma 6 , Kunal Aggarwal 7 , Daniel Brune 8 , Bach-Yen Nguyen 1
Affiliations
Background: This study (NCT05972993) evaluated a novel mRNA vaccine construct using the SARS-CoV-2 BA.5 Spike (S) protein as the model antigen (mRNA-CR-04).
Methods: This first-in-human Phase 1, randomized, placebo-controlled trial enrolled 72 participants in Part A (sentinel vaccination and dose escalation) and 42 in Part B (dose exploration). Adult participants 18-49 years of age were randomized in 3 groups to receive one dose of mRNA-CR-04 (either 10, 30, or 100 µg) or placebo (3:1) in Part A, and 3 µg, 10 µg, or placebo (3:3:1) in Part B. Vaccine safety and immunogenicity in terms of neutralizing titers were assessed until 6 months postinvestigational product administration.
Results: Solicited adverse events (AEs) were mostly mild to moderate and transient. In Part A, Grade 3 reactogenicity was only observed in the 100 µg group (n = 3, 16.7%), and Grade 3 nonsolicited AEs only occurred as causally unrelated serious AEs in 2 participants. No safety concerns deemed causally related to mRNA-CR-04 were raised on review of clinical safety data and clinical laboratory test results. All doses elicited notable neutralizing titers against the vaccine-encoded SARS-CoV-2 BA.5 variant and induced cross-neutralizing titers against the wild type (D614G) variant. The magnitude of the immune response tended to increase with dose. Neutralizing titers waned by Month 6 but remained above baseline levels.
Conclusions: The investigational mRNA-CR-04 vaccine was generally well tolerated, and all doses induced a robust immune response against the encoded antigen at doses ranging between 3 and 100 µg. Further investigation of potential vaccine candidates using this novel mRNA platform is warranted.
Keywords: COVID-19; immunogenicity; mRNA; safety; vaccine.
. 2025 Nov 26;12(12):ofaf689.
doi: 10.1093/ofid/ofaf689. eCollection 2025 Dec. Phase 1 Randomized Controlled Trial of the Safety and Immunogenicity of the SARS-CoV-2 (Omicron BA.5) mRNA-CR-04 Vaccine in Adults 18-49 Years of Age
Abdi Naficy 1 , Mireille Venken 2 , Yingmei Xi 3 , Mark Loughrey 4 , Giulietta Maruggi 5 , Hema Sharma 6 , Kunal Aggarwal 7 , Daniel Brune 8 , Bach-Yen Nguyen 1
Affiliations
- PMID: 41311913
- PMCID: PMC12651558
- DOI: 10.1093/ofid/ofaf689
Background: This study (NCT05972993) evaluated a novel mRNA vaccine construct using the SARS-CoV-2 BA.5 Spike (S) protein as the model antigen (mRNA-CR-04).
Methods: This first-in-human Phase 1, randomized, placebo-controlled trial enrolled 72 participants in Part A (sentinel vaccination and dose escalation) and 42 in Part B (dose exploration). Adult participants 18-49 years of age were randomized in 3 groups to receive one dose of mRNA-CR-04 (either 10, 30, or 100 µg) or placebo (3:1) in Part A, and 3 µg, 10 µg, or placebo (3:3:1) in Part B. Vaccine safety and immunogenicity in terms of neutralizing titers were assessed until 6 months postinvestigational product administration.
Results: Solicited adverse events (AEs) were mostly mild to moderate and transient. In Part A, Grade 3 reactogenicity was only observed in the 100 µg group (n = 3, 16.7%), and Grade 3 nonsolicited AEs only occurred as causally unrelated serious AEs in 2 participants. No safety concerns deemed causally related to mRNA-CR-04 were raised on review of clinical safety data and clinical laboratory test results. All doses elicited notable neutralizing titers against the vaccine-encoded SARS-CoV-2 BA.5 variant and induced cross-neutralizing titers against the wild type (D614G) variant. The magnitude of the immune response tended to increase with dose. Neutralizing titers waned by Month 6 but remained above baseline levels.
Conclusions: The investigational mRNA-CR-04 vaccine was generally well tolerated, and all doses induced a robust immune response against the encoded antigen at doses ranging between 3 and 100 µg. Further investigation of potential vaccine candidates using this novel mRNA platform is warranted.
Keywords: COVID-19; immunogenicity; mRNA; safety; vaccine.