Novavax vs mRNA Vaccines: Understanding Vaccine Reactogenicity
Novavax VP Matthew Rousculp on reactogenicity, vaccine Hesitancy, and supporting informed decisions.
In a real-world US study of frontline health care workers (HCWs) and first responders (FRs), the updated 2024–2025 Novavax (NVX) COVID-19 vaccine was associated with fewer and milder side effects compared to the updated Pfizer-BioNTech (PFZ) mRNA vaccine. The findings, presented at the ESCMID Global Congress 2025, suggest the Novavax vaccine may cause less disruption to work and daily life.
The prospective SHIELD study, conducted at the University of Utah, enrolled 588 participants between September and December 2024 (mean age 36.4 years; 70.1% female). Compared to PFZ recipients, those who received the NVX vaccine reported significantly fewer systemic side effects within 48 hours post-vaccination (73.6% vs 87.5%), fewer symptoms on average (1.7 vs 2.8), and were less likely to experience moderate or severe symptoms (19.2% vs 44.5%).
In the nect part of his interview with Contagion, Matthew Rousculp, vice president at Novavax, provided additional context behind the study findings.
"So there's two components to that," Rousculp said. "So for us, as far as biases, what we want to do is after capturing the data, because again, it's observational, it's not a randomized study. So a prospective observational study, we do have the ability to use statistical diagnostics to go look to say, look, is there a difference between two groups, those who had received the Novavax vaccine versus those who received the mRNA or the Pfizer-BioNTech vaccine? And then also there are methods where you can actually try to control for this."
Rousculp emphasized that while the study was not randomized, the populations were largely comparable at baseline, "We really, really worked hard. What we really saw were that the populations were very, very similar," he explained. "Really didn't see reasons why they were choosing it except for they came in, offered it, and it was just their choice at that time."
Some potential biases, such as participants’ prior experiences with COVID-19 vaccines influencing their selection, could not be fully accounted for, he acknowledged, "We weren't able to control, for example, people's previous experience on the vaccine. Did that impact what vaccine they actually selected? So that we weren't able necessarily to capture," Rousculp said. "But we do see that the results are very consistent with... all those previous studies."
The SHIELD study focused on several dimensions of reactogenicity: incidence, average number of symptoms, severity of symptoms, and impact on daily activities, "The results that came out of the study really were all about trying to understand how burdensome, how bothersome vaccine reactogenicity were for those who had received the COVID-19 vaccine, either the Novavax vaccine or the mRNA vaccine," Rousculp explained. "And so the way we measured that was really those four dimensions."
He continued, "What we saw is there was significant difference in all four of those dimensions. And we saw that the Novavax vaccine was less burdensome than the mRNAs. Again, that's very consistent with previous studies."
Rousculp also pointed to the broader issue of vaccine hesitancy, noting that COVID-19 vaccination rates remain low, particularly among high-risk groups, "We have seen vaccine percentage rates for COVID-19, or what CDC has really reported for this current season, that high-risk populations, for example, 65 years and older, as of this season, only about 30% have been vaccinated with COVID-19 vaccines," he said. "So there's this really big drawback of wanting to be vaccinated."
He emphasized that side effects associated with Novavax's COVID-19 vaccine appear comparable to those seen with high-dose influenza or pneumococcal vaccines, "So how does this reactogenicity of the Novavax vaccine actually compare to other vaccines? There have been some other studies that look at this," he said. "And so really what's being reported is that reactogenicity for the Novavax vaccine is clinically similar to those that receive a high-dose flu vaccine or receive a pneumococcal vaccine."
Ultimately, Rousculp stressed the importance of empowering individuals with data-driven insights to support informed decision-making, "I feel as if for us is that individuals, as they get more information, are able to really kind of make the decisions based upon facts and information that they know are based in research," he said. "And suddenly going about testing, that they can have a very honest conversation with their health care providers, with their family, with their friends."
