N Engl J Med
Next-generation yellow fever vaccine matches gold standard in phase 2 trial
Clinical takeaway: Yellow fever prevention still hinges on vaccination, and a more scalable option could improve access during outbreaks and for travelers. In healthy adults, the investigational vYF vaccine produced immune responses noninferior to YF‑VAX with similar short‑term safety, supporting its potential role in strengthening global vaccine supply.
Yellow fever remains a life‑threatening mosquito‑borne viral infection with no specific antiviral therapy, making vaccination essential for travelers, outbreak control, and residents of endemic regions. While the licensed vaccine (YF‑VAX) is highly effective, its egg‑based manufacturing has repeatedly limited production, forcing dose‑sparing strategies during recent large outbreaks. The investigational vaccine vYF, developed from the same 17D lineage but produced in Vero cells, was designed to overcome supply bottlenecks.
In a phase 2, observer‑blinded trial, 568 healthy adults ages 18 to 60 years of age were randomized to receive a single dose of vYF or YF‑VAX. By day 29, 99.7% of vYF recipients achieved seroconversion, compared with 99.4% in the YF‑VAX group, meeting prespecified noninferiority criteria (difference 0.3 percentage points). Neutralizing antibody titers were similar between groups, peaking at day 29 and declining gradually through 1 year.
Safety outcomes were also comparable. Solicited adverse events occurred in 56.7% of vYF recipients vs. 61.1% with YF‑VAX, while unsolicited events were reported in 26.1% and 21.0%, respectively, with no major safety signals identified.
“This vaccine was developed to address real‑world limitations of supply while maintaining the proven effectiveness of the 17D platform,” the authors wrote, highlighting vYF’s potential value in future epidemic response.
Source: Feroldi E, et al; vYF Vaccine Study Team. (2026, April 9). N Engl J Med. Immunogenicity and safety of vYF, a yellow fever vaccine — A phase 2 trial.