Maternal RSV Vaccines Show Promise for Infant Protection but Raise Safety Concerns
New meta-analysis at the 2025 vaccinology conference highlights the efficacy of maternal RSV vaccines, with calls for enhanced monitoring following safety issues with one candidate
Maternal RSV vaccines have shown effectiveness in preventing lower respiratory tract infections and RSV-related hospitalizations in infants, according to a new meta-analysis presented at the 2025 Annual Conference on Vaccinology Research. However, safety concerns associated with one vaccine candidate have led to calls for enhanced monitoring in future maternal vaccine trials.
The study, led by researchers from Emory University, the University of Siena, and Georgia State University, synthesized data from six randomized controlled trials involving more than 12,600 pregnant women and their infants. While the analysis found encouraging protective benefits for infants, one candidate, GSK's RSVPreF3-mat vaccine, was linked to a 37% increase in preterm birth rates, prompting a pause in its development.
“There is currently no specific biological explanation for the increased risk in preterm births observed with the GSK vaccine,” said Mahmud Sheku, MPH, MSc, one of the study’s co-investigators. “That issue is still under investigation. We may need to look at host factors such as genetic predisposition, pre-existing metabolic conditions, or a history of preterm birth.”
Sheku emphasized the need for future maternal vaccine trials to include more robust surveillance for preterm birth as a predefined outcome. “Developers should consider enhanced monitoring and possibly include preterm birth as a primary or secondary endpoint, especially in early-phase trials like Phase II,” he said.
Among the vaccine candidates evaluated, WyethLederle’s RSV-PFP-2 vaccine was associated with a 50% reduction in medically attended RSV-related lower respiratory tract infections and a 63% reduction in hospitalizations among infants under six months. Other candidates showed mixed results. NANOVAX, for example, was discontinued due to lack of sufficient efficacy in early infancy.
The Pfizer RSVpreF vaccine, which was approved for use in pregnant individuals between 32 and 36 weeks of gestation, currently stands as the only licensed maternal RSV vaccine on the market. According to Sheku, this presents a new set of challenges for ongoing research and product development.
“Now that we have an approved vaccine, developers have to consider the competitive landscape,” he said. “To justify investing in a new product, it has to demonstrate superior efficacy and safety. That’s been difficult for other candidates, especially those associated with adverse outcomes like preterm birth.”
In addition to market forces, Sheku pointed to legal and public perception issues as barriers. “With maternal vaccines, you're dealing with two lives, the mother and the infant. Any perceived safety issue can lead to heightened litigation risk,” he said. “The public also tends to respond more emotionally to safety concerns in maternal immunization than in other contexts, which influences developer decisions.”
The meta-analysis reported no significant differences in serious adverse events for mothers or infants across most studies. However, a slight but statistically significant increase in local adverse reactions, such as pain and swelling at the injection site, was observed.
As RSV vaccines approach broader regulatory review and use, the authors of the study recommended strengthened post-marketing surveillance and continued collection of safety data, particularly on outcomes like preterm birth.
“We have to ask ourselves: what other prevention strategies could offer comparable health and economic benefits to vaccines?” Sheku concluded. “Clear communication around the vaccine development process and risk-benefit decisions is critical. If a vaccine’s benefits outweigh the risks, it may be approved. If the risks are greater, it won’t make it to market. That’s how science and regulation work, and the public deserves to understand that.”
