Novavax COVID-19 Vaccine Linked to Fewer Side Effects in Health Care Workers and First Responders
At ESCMID 2025, SHIELD study data show Novavax recipients experienced fewer side effects and missed less work compared to those who received the Pfizer-BioNTech COVID-19 vaccine.
In a real-world study of frontline health care workers (HCWs) and first responders (FRs) in the United States, recipients of the updated 2024–2025 Novavax (NVX) COVID-19 vaccine reported fewer and less severe side effects than those who received the updated Pfizer-BioNTech (PFZ) mRNA vaccine. These findings suggest the Novavax vaccine may cause less disruption to work and daily life activities.
The prospective SHIELD study, presented at ESCMID and conducted at the University of Utah between September and December 2024, specifically targeted HCWs and FRs, a critical population for pandemic response. Among 588 participants (mean age 36.4 years, 70.1% female), NVX recipients reported significantly fewer systemic reactogenicity events within 48 hours post-vaccination compared to PFZ recipients (73.6% vs. 87.5%). NVX recipients also experienced fewer systemic symptoms on average (1.7 vs. 2.8) and were less likely to have symptoms rated as moderate or severe (19.2% vs. 44.5%).
Matthew Rousculp, vice president at Novavax, explained the motivation behind the study, "The intent of the study was really to try to understand, is there a difference in reactogenicity, or really what we talk about these mild side effects that occur after being vaccinated between COVID-19 vaccines."
Importantly, the study also measured how adverse events impacted participants’ ability to work and engage in daily activities. NVX recipients missed fewer hours of work or daily tasks (0.7 hours vs. 1.4 hours for PFZ recipients) and reported fewer hours of reduced productivity (0.8 hours vs. 2.4 hours).
Using the Sheehan Disability Index, researchers found that 54.3% of NVX recipients reported no impact on work or school activities, compared to 39.3% of PFZ recipients. Similarly, 72.6% of NVX recipients reported no impact on social or leisure activities, versus 57.5% among PFZ recipients.
Rousculp emphasized that the study was designed with clinicians in mind, "Really at the end of the day, it's a study that was predominantly 20% physicians, 20% nurse practitioners or nurses. 83% percent worked in hospitals. So these results are really relevant for the practicing clinician."
He noted that health care workers are often key sources of information for vaccine-hesitant patients, making their personal experiences particularly influential, "We know that healthcare workers are the prime source of information for individuals who have a form of hesitancy... really being able to talk with some authoritarian perceptions is very vital."
The SHIELD study assessed four dimensions of reactogenicity: the presence of systemic and local symptoms (such as fever or injection site pain), the number of simultaneous adverse events, severity graded as moderate or severe (Grade 2 or 3), and the impact on daily activities.
"We just want to say the percent who experienced [symptoms], how many of those adverse events did you experience at the same time, how severe they were, and whether it impacted work, family time, or leisure events," Rousculp explained.
While acknowledging the limitations of observational studies, such as potential self-reporting bias, the SHIELD findings reinforce earlier data suggesting that protein-based COVID-19 vaccines like Novavax's may be associated with lower burdens of side effects compared to mRNA vaccines.
Ultimately, Rousculp emphasized that these findings are intended to empower both clinicians and patients in shared decision-making about vaccination choices, "With that information, it's really going to be very much at the physician level, as well as the patient level, to really kind of make the decision as far as what might be the best option."
In other recent news, the FDA has requested that Novavax conduct an additional clinical trial for its updated COVID-19 vaccine, NVX-CoV2601, delaying its full approval beyond the original April 1, 2025, deadline. Despite earlier optimism from Novavax that its Biologics License Application was approvable, intervention by new Department of Health and Human Services leadership and concerns over the vaccine’s composition led to the request for new data. Interim results from a phase 2/3 study showed that NVX-CoV2601, targeting the Omicron XBB.1.5 variant, produced significantly higher neutralizing antibody responses and maintained a manageable safety profile, supporting its potential as an effective booster. Novavax remains in negotiations with the FDA regarding the size and scope of the new trial.
