Abstract
Highly pathogenic avian influenza A(H5) viruses pose a substantial threat to the health of wild and domestic birds and mammals globally, including humans, underscoring their pandemic potential. The antigenic evolution of the H5 HA poses challenges for pandemic preparedness and vaccine design. Here, the global antigenic evolution of H5 HA was captured in a high resolution antigenic map. To this end, we applied synthetic biology and reverse genetics to complete a virus panel with >130 HA genes representative of the A(H5) viruses that circulated around the world over the last 60 years. We also raised >30 ferret antisera against a representative virus subset. We generated cross-hemagglutination inhibition data and created “antigenic maps” using multidimensional scaling algorithms. The maps revealed clear discordance between the genetic and antigenic evolution of H5 HA and highlighted the rapid antigenic evolution of viruses of the A/Goose/Guangdong/96 lineage. Nevertheless, the antigenic diversity in the map has not expanded substantially since 2010. We used the antigenic maps to engineer immunogenic and “antigenically central” vaccine HA antigens, eliciting antibody responses that are broadly cross-reactive across H5 antigenic space. In ferrets, a designed immunogenic central antigen protected as well as homologous vaccines against heterologous challenge with antigenically highly 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. Currently, preclinical and human clinical studies are ongoing with an mRNA vaccine encoding the antigenically central designer H5 antigen.
Co-Author(s)
Adinda Kok1, Samuel H. Wilks2, Sina Tureli2, Sarah L. James2, Theo M. Bestebroer1, David F. Burke2, Mathis Funk1, Stefan van der Vliet1, Monique I. Spronken1, Willemijn F. Rijnink1, David Pattinson2, Dennis de Meulder1, Miruna E. Rosu1, Pascal Lexmond1, Judith M.A. van den Brand3, Sander Herfst1, Derek J. Smith2, Ron A.M. Fouchier1, Mathilde Richard1. 1 Department Viroscience, Erasmus MC Rotterdam, Netherlands. 2 Center for Pathogen Evolution, University of Cambridge; United Kingdom. 3 Division of Pathology, Faculty of Veterinary Medicine, Utrecht University, Netherlands
Abstract Category
Avian influenza in mammals, pandemic preparedness, and one health