Real-world effectiveness and safety of protein-based and mRNA COVID-19 vaccines (BEEHIVE trial).

Background

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.

Methods

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.

Results

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.

Conclusions

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.