Year: 2025
Type: article
Abstract: Description Influenza Viruses (IV) use haemagglutinin (HA) to bind sialic acid (SA) on cell receptors for infection. While mutations, antigenic drifts and shifts which allow for IV to cross species, become more pathogenic, evade the immune system and give rise to new strains occur on HA, SA binding is conserved. This makes the HA SA-binding region an attractive target for a universal HA inhibitor. We report sialylated (Sia) IgG1 derived crystallisable fragments (Fc, SiaFcs) which bind IVA H1, H3, H5, H7 and IVB HA subtypes, and H1N1 and H3N2 pandemic strains, paving the way for a pan-IV inhibitor. Harnessing receptor mimicry, N- and O-glycosylation sequences were introduced at the N and/or C terminals of IgG1 Fcs fused to the 18 amino acid tailpiece of IgM to inhibit IV entry. These SiaFcs fit into one HA or two nearby HAs, occupying the HA SA-binding region preventing the entry of H1N1pdm09 and H3N2 viruses into cells. SiaFcs will be tested on current BirdFlu bovine H5N1 and avian H7N9. Influenza is a looming threat due to the constant evolution of IVs to adapt, produce new strains and evade current antiviral and vaccination strategies. By targeting the conserved SA binding required by IVs to cause infection, a pan-strain IV inhibitor provides an essential tool to control sudden outbreaks and pandemics. Since IgG is produced by various species, zoonotic infections can also be possibly addressed. Funding Sources Funded by UK Medical Research Council (MRC) GAP fund OPP089 Topic Categories Vaccines and Immunotherapy (VAC)
Source: The Journal of Immunology
Institution: Liverpool School of Tropical Medicine
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funder: Medical Research Council
OpenAlex ID: W4416447133
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