Publication date: Jul 22, 2026
Real-world vaccine effectiveness (VE) and relative VE (rVE) data of protein-based and mRNA COVID-19 vaccines against symptomatic SARS-CoV-2 infections inform policy recommendations and reinforce public confidence. The study aim was to assess the safety and VE of the 2023-2024 protein-based and mRNA COVID-19 vaccines (XBB. 1.5) in a real-world setting. The single-site, pragmatic BEEHIVE clinical trial was conducted among participants aged ≥18 years from the Salt Lake City, Utah, area, who had previously received ≥2 mRNA COVID-19 vaccines, from November 17, 2023, through September 9, 2024. Randomized participants received a protein-based or mRNA COVID-19 vaccine in a double-blind manner. An unblinded, nonrandomized comparator control group that did not receive a study vaccine was also enrolled. The primary aim measured VE between the randomized and comparator groups. The secondary aim was to measure rVE between the 2 vaccine platforms. In the modified intention-to-treat (mITT) analysis, VE and rVE were estimated using a proportional-hazards model for symptomatic infections confirmed by weekly self-administered rapid antigen tests (RATs) over 24 weeks, adjusted for covariates. Reactogenicity and treatment-emergent adverse events (TEAEs) were recorded. Randomized cohorts (N = 909; protein-based, n = 452; mRNA, n = 457) were largely well-balanced with some differences in baseline covariates versus the comparator group (n = 279), mostly age-related. The mITT population had 142 RAT-confirmed symptomatic SARS-CoV-2 cases with an adjusted VE of 43. 6% (95% CI, 18. 3-61. 0); rVE (protein-based vs mRNA) was -26. 7% (90% CI, -78. 6% to 10. 1%) and did not reach statistical significance. Safety and reactogenicity were comparable to previously reported findings, with no serious study vaccine-related TEAEs, myocarditis/pericarditis, hospitalization, or death. This is one of the earliest real-world trials evaluating the VE of the 2023-2024 COVID-19 vaccines (XBB. 1.5). These results suggest that both protein-based and mRNA vaccines are well-tolerated and significantly reduce the risk of symptomatic SARS-CoV-2 infections.
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| Concepts | Keywords |
|---|---|
| Beehive | COVID-19 |
| Myocarditis | mRNA COVID-19 vaccine |
| Utah | Protein-based COVID-19 vaccine |
| Vaccine | Reactogenicity |
| Tolerability | |
| Vaccine efficacy |
Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | SARS-CoV-2 infections |
| disease | MESH | infections |
| disease | MESH | myocarditis |
| disease | MESH | pericarditis |
| disease | MESH | death |