Analysis of HA5 Hemagglutinins from Influenza A Viruses for Mass-Charge Patterns to Understand Antigenic Drift Related to Immune Escape

Influenza A viruses remain a persistent global health threat due to their ability to mutate and evade host immune defences, a process largely driven by changes in hemagglutinin (HA). HA is a glycoprotein present on the surface of influenza virions and plays a critical role in viral entry into host cells by binding to cellular receptors. In this study, 23 HA5 protein sequences from various influenza viral strains collected from wild birds, seagulls, ducks, geese, and chickens, as well as from humans in mainland China during the period from 2023 to 2024, were analyzed for mass-charge patterns by our predictive modelling algorithm to understand the nonlinear trend of viral evolution, particularly regarding their antigenic drift and immune escape potential. Two critical regions in HA5 proteins were identified and analyzed. The first region is a “mutable zone” (the negative gravity centre identified by mass-charge pattern analysis), which frequently accumulates multiple mutations. This leads to antigenic drift and instability, enabling the virus to evade pre-existing herd immunity. Analyzing and monitoring mass-charge changes may help predict the evolutionary trend of the viruses and the emergence of future variants in these regions where the viruses were collected, thereby informing the design and development of vaccines for the viruses analyzed and related strains. The second region is a “stable core” (positive gravity centre), a highly conserved region essential for viral function. Due to its conservation across strains, it may represent a promising target for developing universal vaccines and broad-spectrum antibodies capable of conferring protection against multiple variants simultaneously for the viruses analyzed and related strains. In summary, our analyses, with a predictive modelling algorithm for mass-charge patterns of HA5 protein sequences, provide a novel metric for viral evolution and evaluating the immune evasion potential, and offer a strategic framework for designing vaccines against the viruses analyzed and related strains.