Inhaled ACE2 decoy

The emergence of SARS-CoV-2 variants with highly mutated spike proteins has presented an obstacle to the use of monoclonal antibodies for the prevention and treatment of SARS-CoV-2 infection. We show that a high-affinity receptor decoy protein in which a modified ACE2 ectodomain is fused to a single domain of an immunoglobulin heavy chain Fc region dramatically suppressed virus loads in mice upon challenge with a high dose of parental SARS-CoV-2 or Omicron variants. The decoy also potently suppressed virus replication when administered shortly post-infection. The decoy approach offers protection against the current viral variants and, potentially, against SARS-CoV-2 variants that may emerge with the continued evolution of the spike protein or novel viruses that use ACE2 for virus entry.

Objective To investigate the effects of tolerogenic dendritic cells (tolDCs) induced by nuclear factor κB oligodeoxynucleotide decoy (NF-κB ODN decoy) on Th1 cells, Th2 cells, Th17 cells and regulatory T cells (Tregs) and the intervention effects on collagen-induced arthritis (CIA) rats. Methods SD female rats used to establish CIA rat models were divided into four groups, including a CIA model group, a bovine type II collagen-decoy-dendritic cell (Col2-decoy DC) treatment group, a blank control group, and a Col2-decoy DC control group. On the 20th days after the first immunization, the rats were injected with tolDCs via the tail vein, and the rats were sacrificed on the 7th weeks. The proportions of Th1 cells, Th2 cells, Th17 cells, and Tregs in the rat spleen were detected by flow cytometry. The ankle joint pathomorphological change was evaluated by HE staining, and the arthritis index (AI) was scored. Results Compared with the CIA model group, the Col2-decoy DC group had lower AI and milder ankle joint pathomorphological change. The percentages of Th1 cells and Th17 cells in the spleen CD4⁺ T cells decreased, while the percentages of Th2 cells and Tregs increased. Conclusion The treatment of tolDCs can alleviate the inflammation and arthropathy of CIA rats by reducing the proportion of Th1 and Th17 cells in CD4⁺ T cells.