Our current assays to determine the receptor specificity and vaccine efficiency of influenza A virus fail as they do not represent receptors available in the human upper respiratory tract. The lack of these receptors in our laboratory hosts to create vaccines significantly dampen yields, the resulting mismatched vaccines do not afford proper protection and further drive antigenic drift.
The objective of our research is to elucidate the functional receptor of zoonotic and antigenically drifting influenza A viruses. Using these zoonotic and antigenically drifted viruses on our novel glycan arrays, we try to understand how glycan specificity changes due to host switching and immune pressure.
To achieve this goal, we enzymatically synthesize complex glycans including sialic acid and LacNAc modifications that are found on respiratory tract epithelial cells of humans and other IAV hosts. After synthesis, these complex glycans are printed on glass slide and interrogated with influenza A viruses to analyze evolving receptor specificities.
Our results reveal that our glycan array set up is well suited to analyze avian and human-type receptor specificities, NeuAc vs NeuGc binding and demonstrated that H5 viruses from chicken origin, prefer sialylated Lewis X structures. Importantly, human viruses appeared to have changed their receptor binding phenotype to complex N-glycans containing multiple LacNAc repeats.
We conclude that the lack of complex N-glycan receptors in standard laboratory assays is a bottleneck for proper analyses of drifting human viruses