Kok Adinda, Wilks Samuel H, Tureli Sina, James Sarah L, Bestebroer Theo M, Burke David F, Funk Mathis, van der Vliet Stefan, Spronken Monique I, Rijnink Willemijn F, Pattinson David, de Meulder Dennis, Rosu Miruna E, Lexmond Pascal, van den Brand Judith M A, Herfst Sander, Smith Derek J, Fouchier Ron A M, Richard Mathilde
Department of Viroscience, Erasmus University Medical Center; Rotterdam, The Netherlands.
Center for Pathogen Evolution, University of Cambridge; Cambridge, United Kingdom.
bioRxiv. 2024 Aug 6:2024.08.06.606696. doi: 10.1101/2024.08.06.606696.
Highly pathogenic avian influenza A(H5) viruses globally impact wild and domestic birds, and mammals, including humans, underscoring their pandemic potential. The antigenic evolution of the A(H5) hemagglutinin (HA) poses challenges for pandemic preparedness and vaccine design. Here, the global antigenic evolution of the A(H5) HA was captured in a high-resolution antigenic map. The map was used to engineer immunogenic and antigenically central vaccine HA antigens, eliciting antibody responses that broadly cover the A(H5) antigenic space. In ferrets, a central antigen protected as well as homologous vaccines against heterologous infection with two antigenically distinct viruses. This work showcases the rational design of subtype-wide influenza A(H5) pre-pandemic vaccines and demonstrates the value of antigenic maps for the evaluation of vaccine-induced immune responses through antibody profiles.
高致病性甲型H5禽流感病毒在全球范围内对野生和家养禽类以及包括人类在内的哺乳动物产生影响，凸显了其大流行潜力。甲型H5血凝素（HA）的抗原进化给大流行防范和疫苗设计带来了挑战。在此，甲型H5 HA的全球抗原进化情况在一张高分辨率抗原图谱中得以呈现。该图谱被用于设计具有免疫原性且位于抗原中心的疫苗HA抗原，引发的抗体反应能广泛覆盖甲型H5抗原空间。在雪貂身上，一种位于抗原中心的抗原对两种抗原性不同的病毒的异源感染提供了与同源疫苗相同的保护。这项工作展示了甲型H5大流行前疫苗的全亚型合理设计，并证明了抗原图谱通过抗体谱评估疫苗诱导免疫反应的价值。
