Persistence of the neutralizing antibody response one year after a single injection of a new Yellow fever vaccine in adults

Abstract

Introduction

Yellow fever (YF) remains a major global health threat, complicated by climate change, vector expansion, and insufficient health system infrastructure in endemic regions. Recent shortages of licensed vaccines during regional outbreaks underscore the need for next-generation YF vaccines that retain safety and effectiveness standards while enhancing manufacturing efficiency. Grown in serum-free Vero cells, vYF is a live-attenuated YF vaccine developed to ensure a sustainable and robust global supply.

Methods

In two ongoing Phase II randomized, observer-blind, active-controlled, non-inferiority multicenter clinical trials of vYF in 18-60-year-old adults in the US (vs. YF-VAX – VYF02 study) or in Europe and Asia (vs. Stamaril – VYF03 study), the neutralizing antibody (NAb) responses are being measured by a YF microneutralization assay on day 29 (D29), month 6 (M6), and then annually from year 1 (Y1) until Y5. Seroprotection is defined as NAb titers ≥ 10 (1/dil). Interim analyses conducted one-month post-vaccination demonstrated that the vYF immune response was non-inferior to YF-VAX or Stamaril. Here, we report the immunogenicity up to Y1.

Adults were randomized 2:1 to receive one dose of vYF or YF active control: 568 in the US (VYF02) and 690 in Europe and Asia (VYF03).

Results

Twenty-eight days after a vYF dose administration, over 99% of YF-naive participants in the US, and over 98% in the EU and over 95% in Asia were seroprotected.

YF-naive recipients (FAS) exhibited D29 post-vaccination geometric mean titers (GMT) well above the seroprotective threshold: 2654, 1/dil, in the US; 2508, 1/dil, in EU; 1374, 1/dil, in Asia. As expected, GMTs waned after D29 but more than 97% of participants in the US, over 98% in Europe and more than 94% in Asia maintained titers above the threshold of protection at Y1, with GMTs of 401, 1/dil, in the US; 469, 1/dil, in EU; and 205, 1/dil, in Asia.

Discussion

Overall, 94% or more of YF-naive adults in US, EU and Asia were seroprotected 28 days after receiving vYF and remained seroprotected at Y1. Seroprotection rates and GMT values following administration of the control vaccines (YF-VAX or Stamaril) were in similar ranges at all evaluated timepoints. Despite lower NAb titers observed in Asia from D29, GMT values remain well above the threshold considered for protection in all regions.

Conclusion

Immunogenicity of vYF is non-inferior to YF-VAX and Stamaril, inducing seroprotective NAb responses in 18 to 60-year-old vaccinees to 1-year post-vaccination. Reduced NAb titers in Asia relative to the US and Europe did not diminish rates of seroprotection. These results are encouraging for addressing unmet public health needs during YF outbreaks.