Antigenic mapping guides broad influenza A(H5) vaccine design

Rapidly evolving viruses, such as influenza, present challenges for vaccine design. Influenza A(H5) viruses are of particular concern because they circulate in birds and are increasingly spreading among mammals, leading to antigenic diversification that requires constant updating of vaccine candidates to prepare for a pandemic. In an article now published in NatureKok et al. analyzed the antigenic evolution of A(H5) viruses and used this information to design vaccine antigens that elicit broader immunity.

The authors constructed a map tracing the antigenic evolution of influenza A(H5) viruses from 1959 to 2022 and hypothesized that antigens near the center of the map would elicit broader immune responses, providing a starting point for the design of cross-reactive vaccine candidates. To this end, they selected several wild-type antigens located near the center of the map and refined their positioning through targeted modifications. This yielded three core vaccine antigen candidates. One candidate, called CVA-Anhui, showed the broadest reactivity, including against viruses from genetic clades currently circulating, and was selected for testing in ferrets.