Novavax JN.1 COVID-19 Vaccine Linked to Fewer Side Effects Than mRNA in Health Care Workers

Preliminary data from the SHIELD-Utah study suggest that the Novavax COVID-19 Vaccine, Adjuvanted (2024–2025 formula), was associated with lower reactogenicity compared with the Pfizer-BioNTech mRNA COVID-19 vaccine targeting the same JN.1 variant.1

In October 2024, the US FDA granted emergency use authorization for the updated Novavax COVID-19 vaccine targeting the JN.1 variant for individuals aged 12 years and older. The authorization allowed for the inclusion of the protein-based option in the fall 2024 vaccination campaign and provided an alternative for those who may prefer or require a non-mRNA platform.2

The prospective, real-world interventional study (NCT06633835) was conducted at University of Utah Health between September and December 2024. Participants—primarily health care workers and first responders—self-selected to receive either the Novavax or Pfizer-BioNTech vaccine and completed follow-up surveys 2 and 7 days post-vaccination. Survey data included local and systemic reactogenicity symptoms as well as impact on daily functioning, including work-related productivity.3

Among the 588 participants (219 Novavax; 369 Pfizer-BioNTech), those receiving the Novavax vaccine reported fewer systemic symptoms on average (1.7 vs 2.8). Moderate or greater severity (grade ≥2) symptoms were reported in 24.2% of Novavax recipients compared with 43.8% of Pfizer-BioNTech recipients. Local reactogenicity events also occurred less frequently in the Novavax group (absolute difference, –12.5%).1

"The risk of side effects or reactogenicity has been shown to be a major decision factor for those opting to get vaccinated. Our findings of lower frequency and intensity of reactogenicity symptoms from the protein-based COVID-19 vaccine observed in SHIELD-Utah add valuable insights to the public debate weighing choice and value of COVID-19 vaccination," principle investigator Sarang K. Yoon, DO, MOH, University of Utah Health, said in a press release.1

Impact on daily activities differed between groups. Mean hours of missed work were lower in the Novavax cohort (0.7 vs 1.4 h), as were hours of reduced productivity (0.8 vs 2.4 h).1

Participants included physicians (20.4%), nurses and nurse practitioners (19.2%), and medical assistants (11.9%).1

These findings, presented at the 2025 Congress of the European Society of Clinical Microbiology and Infectious Diseases, underscore potential tolerability advantages of the protein-based, adjuvanted Novavax platform relative to mRNA formulations. According to study investigators, reactogenicity remains a key consideration in patient decision-making around COVID-19 vaccination. Full study results are expected to be submitted for peer-reviewed publication later this year.1

"Our protein-based nanoparticles and Matrix-M adjuvant are the foundation of our COVID-19 vaccine," Ruxandra Draghia-Akli, MD, PhD, executive vice president and head of research and development at Novavax, said in the release.1 "Our new R&D pipeline is focused on delivering more assets built on this powerful technology platform, including the use of our Matrix M adjuvant, which has been associated with a favorable tolerability profile."

References:

1. SHIELD-Utah study shows Novavax's COVID-19 vaccine induces lower reactogenicity symptoms compared to mRNA. News item. Novavax. April 15, 2025. Accessed April 22, 2025. https://ir.novavax.com/press-releases/2025-04-15-SHIELD-Utah-Study-Shows-Novavaxs-COVID-19-Vaccine-Induces-Lower-Reactogenicity-Symptoms-Compared-to-mRNA

2. Jennings S. FDA Grants Emergency Use Authorization for Updated Novavax COVID-19 Vaccine. Patient Care Online. September 3, 2024. https://www.patientcareonline.com/view/fda-grants-emergency-use-authorization-for-updated-novavax-covid-19-vaccine

3. A Study of BNT162b2 RNA-Based Vaccine Candidates Against COVID-19 in Healthy Adults. ClinicalTrials.gov. Identifier: NCT06633835. https://clinicaltrials.gov/study/NCT06633835. Published October 3, 2023. Accessed April 22, 2025.