Cross-Neutralizing and Broadly Neutralizing Human Antibodies Against Nonenveloped Viruses

Neutralizing antibodies (NAbs) play a central role in antiviral protection and are increasingly considered for prophylactic or therapeutic use, particularly against viruses lacking effective antiviral treatments. While research has predominantly focused on NAbs targeting the envelope proteins of enveloped viruses, nonenveloped viruses remain major human pathogens for which broad antibody responses are less well characterized. Recent work has identified several cross- and broadly neutralizing antibodies generated during human infection with nonenveloped viruses, revealing different mechanisms of action and new structural vulnerabilities. This review provides an overview of these NAbs, summarizes their mechanisms of action when these have been identified, and highlights recent advances relevant to antiviral antibody development and vaccine research.