Written by |Tang XiaotangNeuraminidase (NA) is a less common but essential surface protein in influenza viruses that excises sialic acid from glycoproteins and glycolipids on the surface of host cells, enabling the release of offspring viruses from infected cells。The catalytic activity of NA is one of the main targets of influenza antiviral drugs, and NA inhibitors have been widely used for more than two decades in human influenza, but our understanding of the NA antigen panpicture is still incomplete. March 1, 2024, National Institute of Allergy and Infectious Diseases, National Institutes of Health, USAmasaru kanekiyoThe team is inimmunityPublished on ** entitledprotective human monoclonal antibodies target conserved sites of vulnerability on the underside of influenza virus neuraminidaseResearch**,Na-specific human monoclonal antibodies were isolated and identified from two H3N2 virus infected individuals, with a panel targeting a conserved epitope at the base of the N2 Na globular head capable of providing protective function in mice
The researchers isolated and identified six monoclonal antibodies (NDS) targeting the Na dark side (NDS) in the peripheral blood mononuclear cells of two H3N2-infected individuals1、nds.1.1、nds.1.2、nds.3、nds.5 and nds6), conserved epitopes of four N2 Na from three seasonal H3N2 viruses and one porcine variant H3N2 (H3N2V) virus. The researchers provided NDS1 and nds3 The structural basis of the complex with NA, found nds1 and ndsThe epitope of 3 is generally conserved in human H3N2 viruses as well as HXN2 viruses. Next, the researchers investigated the function of antibodies targeting NDS, and through NA-based influenza replication inhibition assays and enzyme-linked lectin assays, it was found that antibodies targeting NDS were able to inhibit the catalytic activity of NA by spatial interference with glycoprotein substrates. Antibodies targeting NA typically do not prevent the virus from entering the host cell, but they can prevent the release of newly produced viral particles from infected cells by inhibiting the catalytic activity of NA. Co-incubated with the virus and then added to cells, these antibodies targeting NDS were found to be effective in inhibiting the growth of viruses, including several H3N2 viruses, as well as porcine variants H3N2V and H2N2 viruses. Importantly, the researchers tested the protective function in mice, and in a prophylactic experiment, the researchers administered a monoclonal antibody, NDS., 24 hours prior to the Philippines 2 1982 (H3N2) viral challenge1 Provides complete protection when given at 10 and 3 mg kg and 90% survival when given at the lowest dose of 1 mg kg. nds.1.1 performance with nds1 Similar, providing 80% to 90% protection at all doses tested. nds.3Provides complete protection at doses of 10 and 3 mg kg. When given at the lowest dose, the survival rate is only 10%. The control anti-HA stem monoclonal antibody FI6V3 provided relatively weak protection compared to all tested anti-NA monoclonal antibodies; In the protective experiment, mice were administered 10 mg kg of monoclonal antibody and received NDS. 48 h post-infection1 or nds1.1 in 90% of mice survived and lost about 10% of their body weight. And accept ndsMice with 3** had a 50% survival rate and had more severe weight loss. In this ** setting, the control anti-HA monoclonal antibody Fi6v3 only provided about 30% survival. These results show that monoclonal antibodies targeting NDS exhibit a high degree of protection not only in mice as a preventive measure, but also after exposure. 
In summary, this study describes a class of specific human monoclonal antibodies targeting the NA globular head domain, which are able to effectively inhibit human H3N2, porcine variant H3N2, and H2N2 viruses, and provide prophylactic and post-exposure protection against lethal H3N2 infection in mice, and provide the structural basis of two of these antibodies in NA complexes. This study helps to guide the development of effective strategies against evolving influenza viruses by identifying hidden conserved susceptibility sites at the bottom of NA. Original address:Plate maker: Eleven.
References
1. mcauley, j.l., gilbertson, b.p., trifkovic, s., brown, l.e., and mckimm- breschkin, j.l. (2019). influenza virus neuraminidase structure and func- tions.front. microbiol.10, 39.2. chen, y.-q., wohlbold, t.j., zheng, n.-y., huang, m., huang, y., neu, k.e., lee, j., wan, h., rojas, k.t., kirkpatrick, e., et al. (2018). influenza infection in humans induces broadly cross-reactive and protective neur- aminidase-reactive antibodies.cell173, 417–429.e10.
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