Objectives To compare the percentage of participants that experienced any solicited systemic reactogenicity symptom after one dose of the updated 2024–2025 adjuvanted protein-based Novavax (NVX; JN.1) or Pfizer–BioNTech mRNA (PFZ; KP.2) COVID-19 vaccine within 2- and 7-days post-vaccination and examine its disrupting impact on daily life.

Methods In this prospective, interventional, real-world study (SHIELD/NCT06633835), previously vaccinated healthcare workers (HCWs) and first responders (FRs) from Salt Lake City, Utah, USA, and surrounding areas self-selected to receive NVX or PFZ. At 2- and 7-days post-vaccination, participants self-reported on 11 vaccine-related reactogenicity symptoms and functional impairment using a 5-item modified Sheehan Disability Scale.

Results 588 participants completed the Day 2 questionnaire (NVX, n=219; PFZ, n=369); 583 completed the Day 7 questionnaire (NVX, n=217; PFZ, n=366). Two-days post-vaccination, NVX recipients were less likely to report a systemic (OR=0.40; 95% CI, 0.21–0.75) or local (OR=0.10; 95% CI, 0.30–0.33) reactogenicity symptom and lost 50% fewer work hours (0.7 vs 1.4 h) and 66% fewer productive hours (0.8 vs 2.4 h) than PFZ recipients. There was little to no difference between vaccines at 7-days post-vaccination.

Conclusion Fewer reactogenicity symptoms following COVID-19 vaccination suggest use of the NVX vaccine as an immunization option with a lower disruption to daily life.

SKY has received funding from Novavax, Inc. pertaining to this study and from the Centers for Disease Control and Prevention for prior COVID-19 vaccine studies and has served as an advisory board member, without compensation, for Pfizer-BioNTech. GLE, AP, JM, JG, and RC are funded through a contract agreement with the University of Utah, with prime funding and study drug provided by Novavax, Inc. SC, DO, RZ, LJ, and JC are full-time employees of RTI Health Solutions, an independent nonprofit research organization, which was retained by Novavax, Inc. to conduct the research. BAP is a former employee of RTI Health Solutions. Their compensation is unconnected to the studies on which they work. BH, BW, JF, and MDR are Novavax, Inc. employees or contractors and as such receive a work salary and may hold Novavax, Inc. stock.

NCT06633835

https://www.clinicaltrials.gov/study/NCT06633835

Funding was provided by Novavax, Inc.

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The study protocol, including participant compensation, was approved by the institutional review board (IRB) at the University of Utah (IRB #00181626; ClinicalTrials.gov identifier: NCT06633835).

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Study information is available online at: https://www.clinicaltrials.gov/study/NCT06633835. Requests submitted to the corresponding author will be considered upon publication of this article and de-identified participant data might be provided.