Protective mechanisms of nonneutralizing antiviral antibodies

• Published in: PLoS pathogens 2023-10, Vol.19 (10), p.e1011670-e1011670
• Main Authors: Chandler, Tawny L, Yang, Agnes, Otero, Claire E, Permar, Sallie R, Caddy, Sarah L
• Format: Article
• Language: English
• Subjects: Analysis; Animal models; Animals; Antibodies; Antibodies, Neutralizing; Antibodies, Viral; Antigen presentation; Antiviral Agents; Apoptosis; Biology and Life Sciences; Blocking; Care and treatment; Cell culture; Cytomegalovirus; Cytotoxicity; Dendritic cells; Dengue fever; Diagnosis; Disease prevention; Dosage and administration; Ebola virus; Effector cells; Fc receptors; Glycoproteins; Health aspects; HIV; HIV (Viruses); HIV Antibodies; Human immunodeficiency virus; Humans; Infections; Influenza; Influenza, Human; Marburg virus disease; Medicine and Health Sciences; Pearls; Proteins; Receptors, Fc; Research and Analysis Methods; Rotavirus; Severe acute respiratory syndrome coronavirus 2; Testing; Vaccines; Viral antibodies; Viral diseases; Viral infections; Virus Diseases; Viruses; West Nile virus
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1011670

Antibodies that can bind to viruses but are unable to block infection in cell culture are known as "nonneutralizing antibodies." Such antibodies are nearly universally elicited following viral infection and have been characterized in viral infections such as influenza, rotavirus, cytomegalovirus, HIV, and SARS-CoV-2. It has been widely assumed that these nonneutralizing antibodies do not function in a protective way in vivo and therefore are not desirable targets of antiviral interventions; however, increasing evidence now shows this not to be true. Several virus-specific nonneutralizing antibody responses have been correlated with protection in human studies and also shown to significantly reduce virus replication in animal models. The mechanisms by which many of these antibodies function is only now coming to light. While nonneutralizing antibodies cannot prevent viruses entering their host cell, nonneutralizing antibodies work in the extracellular space to recruit effector proteins or cells that can destroy the antibody-virus complex. Other nonneutralizing antibodies exert their effects inside cells, either by blocking the virus life cycle directly or by recruiting the intracellular Fc receptor TRIM21. In this review, we will discuss the multitude of ways in which nonneutralizing antibodies function against a range of viral infections.