New yellow fever vaccine matches safety and effectiveness of current shot

Yellow fever is a viral disease that is spread to humans through the bites of infected mosquitoes. The symptoms range from mild fever-like aches and pains to severe liver disease with bleeding, often accompanied by yellowing skin and eyes. As of now, we do not have antiviral drugs to cure these diseases, as most of the treatments are limited to easing symptoms. Hence, prevention via vaccination is our best bet against this disease. A recent study has found that a new yellow fever vaccine, called vYF by Sanofi, works just as well as the current licensed vaccine, YF-VAX.

This phase 2 clinical trial included healthy adults aged 18 to 60. Participants were split into two groups: About two-thirds (329) received the new vYF vaccine, while the remaining one-third (156) were given the currently licensed YF-VAX vaccine. Of those who received the new vYF vaccine, 99.7% developed protective antibodies within 28 days. For the YF-VAX group, 99.4% developed antibodies within a month. In both cases, the antibody levels peaked at day 29 and gradually declined over the following year to a comparable level.

The findings are published in The New England Journal of Medicine.

Testing the new vaccine against the approved one

Every year, yellow fever takes away approximately 29,000 to 60,000 lives. The World Health Organization advises vaccination for people living in high-risk areas and for travelers heading there to protect individuals and curb the global spread of yellow fever. Even though safe and effective vaccines exist, outbreaks have continued in recent years, including in Central Africa and Brazil.

One of the most severe outbreaks in two decades occurred between December 2015 and November 2016 in Angola and the Democratic Republic of the Congo, which resulted in a global vaccine shortage. With the world’s emergency supply exhausted, medical workers were forced to use smaller amounts of the vaccine to try to protect more people.

To address this production bottleneck, Sanofi introduced a new version of the yellow-fever vaccine called vYF. This live-attenuated vaccine, which contains a living but significantly weakened version of the yellow fever virus, is grown in Vero cells—a cell line originally isolated from the kidney of an African Green Monkey—making production more efficient and yielding higher yields than the current vaccine.

Early tests of the new vYF vaccine were quite encouraging. In both animal studies and initial human trials, it proved to be safe and sparked a strong immune response, matching that of existing yellow fever vaccines. A phase 1 study also backed these findings up.

In this study, the team designed a rigorous phase 2 clinical trial. The trial was randomized, meaning participants were randomly assigned to receive either the new or existing vaccine, and observer-blind, so the people evaluating the results didn’t know which vaccine each participant had received, a safeguard to ensure the findings were unbiased. Instead of comparing the new vaccine against a placebo, it was tested head-to-head against an already approved vaccine.

The study found that the new vYF vaccine performs on par with the current standard, YF-VAX, in both safety and effectiveness. No major safety issues were flagged, and side effects were similar between the two—mostly mild, such as headaches or soreness at the injection site. Importantly, no participants had to withdraw from the study because of side effects.

Once the vaccine clears the next steps and gains approval, the world will be better equipped to tackle yellow fever outbreaks, with a valuable new tool at our disposal.

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