title: Genetic and structural determinants of virus neutralizing antibodies.
abstract: Neutralizing antibodies (Abs) are the principal protective mechanism against disease caused by reinfection with viruses. Ab-mediated neutralization of viruses is a complex process comprising multiple mechanisms. Every structural aspect of Abs is potentially capable of modulating the level of neutralizing activity or the mechanisms of neutralization. The focus of our laboratory is to understand the genetic and structural basis of Ab-mediated neutralization of human viral pathogens. We demonstrated the unexpected finding that virus antigen-binding fragments of Abs (Fabs) mediate potent virus neutralizing effects in vivo. This work has led to a broad investigation of the importance of the genetics, chemistry, and structure of the combining site to the neutralizing activity of antiviral Abs. Ongoing work in our laboratory reveals that effect or functions specified by the Ab isotype such as polymer formation, interactions with complement, interactions with Fc receptors, and the ability to transcytose mucosal epithelia, also modulate the mechanism and level of neutralizing effects mediated by antiviral Abs.
authors.affiliation: Department of Pediatrics and Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232-2581, USA. james.crowe@vanderbilt.edu
authors.forename: J E
authors.initials: JE
authors.lastname: Crowe
authors.forename: R O
authors.initials: RO
authors.lastname: Suara
authors.forename: S
authors.initials: S
authors.lastname: Brock
authors.forename: N
authors.initials: N
authors.lastname: Kallewaard
authors.forename: F
authors.initials: F
authors.lastname: House
authors.forename: J H
authors.initials: JH
authors.lastname: Weitkamp
mesh_terms: D000914:Antibodies, Viral / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D000915:Antibody Affinity; D000916:Antibody Diversity; D000956:Antigens, Viral / Q000276:immunology; D016764:Cell Polarity; D000939:Epitopes / Q000276:immunology; D019143:Evolution, Molecular; D005803:Genes, Immunoglobulin; D006801:Humans; D007113:Immunity, Innate; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007158:Immunologic Techniques; D009092:Mucous Membrane / Q000276:immunology; D009500:Neutralization Tests; D012136:Respiratory Syncytial Viruses / Q000276:immunology / Q000502:physiology; D013329:Structure-Activity Relationship; D014771:Virion / Q000276:immunology; D014779:Virus Replication / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D000939:Epitopes; D007140:Immunoglobulin Fab Fragments; D007132:Immunoglobulin Isotypes; D007135:Immunoglobulin Variable Region