Antibody protection from SARS-CoV-2 respiratory tract exposure and infection.

The COVID-19 pandemic has underscored the need to understand the dynamics of SARS-CoV-2 respiratory infection and protection provided by the immune response. SARS-CoV-2 infections are characterized by a particularly high viral load, and further by the small number of inhaled virions sufficient to generate a high viral titer in the nasal passage a few days after exposure. SARS-CoV-2 specific antibodies (Ab), induced from vaccines, previous infection, or inhaled monoclonal Ab, have proven effective against SARS-CoV-2 infection. Our goal in this work is to model the protective mechanisms that Ab can provide and to assess the degree of protection from individual and combined mechanisms at different locations in the respiratory tract. Neutralization, in which Ab bind to virion spikes and inhibit them from binding to and infecting target cells, is one widely reported protective mechanism. A second mechanism of Ab protection is muco-trapping, in which Ab crosslink virions to domains on mucin polymers, effectively immobilizing them in the mucus layer. When muco-trapped, the continuous clearance of the mucus barrier by coordinated ciliary propulsion entrains the trapped viral load toward the esophagus to be swallowed. We model and simulate the protection provided by either and both mechanisms at different locations in the respiratory tract, parametrized by the Ab titer and binding-unbinding rates of Ab to viral spikes and mucin domains. Our results illustrate limits in the degree of protection by neutralizing Ab alone, the powerful protection afforded by muco-trapping Ab, and the potential for dual protection by muco-trapping and neutralizing Ab to arrest a SARS-CoV-2 infection. This manuscript was submitted as part of a theme issue on "Modelling COVID-19 and Preparedness for Future Pandemics".

LPS-binding IgG arrests actively motile Salmonella Typhimurium in gastrointestinal mucus.

The gastrointestinal (GI) mucosa is coated with a continuously secreted mucus layer that serves as the first line of defense against invading enteric bacteria. We have previously shown that antigen-specific immunoglobulin G (IgG) can immobilize viruses in both human airway and genital mucus secretions through multiple low-affinity bonds between the array of virion-bound IgG and mucins, thereby facilitating their rapid elimination from mucosal surfaces and preventing mucosal transmission. Nevertheless, it remains unclear whether weak IgG-mucin crosslinks could reinforce the mucus barrier against the permeation of bacteria driven by active flagella beating, or in predominantly MUC2 mucus gel. Here, we performed high-resolution multiple particle tracking to capture the real-time motion of hundreds of individual fluorescent Salmonella Typhimurium in fresh, undiluted GI mucus from Rag1-/- mice, and analyzed the motion using a hidden Markov model framework. In contrast to control IgG, the addition of anti-lipopolysaccharide IgG to GI mucus markedly reduced the progressive motility of Salmonella by lowering the swim speed and retaining individual bacteria in an undirected motion state. Effective crosslinking of Salmonella to mucins was dependent on Fc N-glycans. Our findings implicate IgG-mucin crosslinking as a broadly conserved function that reduces mucous penetration of both bacterial and viral pathogens.