title: Rotavirus enterotoxin NSP4 has mucosal adjuvant properties.
abstract: Rotavirus nonstructural protein 4 (NSP4) is a protein with pleiotropic properties. It functions in rotavirus morphogenesis, pathogenesis, and is the first described viral enterotoxin. Since many bacterial toxins function as potent mucosal adjuvants, we evaluated whether baculovirus-expressed recombinant simian rotavirus SA11 NSP4 possesses adjuvant activity by co-administering NSP4 with keyhole limpet hemocyanin (KLH), tetanus toxoid (TT) or ovalbumin (OVA) as model antigens in mice. Following intranasal immunization, NSP4 significantly enhanced both systemic and mucosal immune responses to model immunogens, as compared to the control group, in an antigen-specific manner. Both full-length and a cleavage product of SA11 NSP4 had adjuvant activity, localizing this activity to the C-terminus of the protein. NSP4 forms from virulent and avirulent porcine rotavirus OSU strain, and SA11 NSP4 localized within a 2/6-virus-like particle (VLP) also exhibited adjuvant effects. These studies suggest that the rotavirus enterotoxin NSP4 can function as an adjuvant to enhance immune responses for a co-administered antigen.
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Owen V
authors.initials: OV
authors.lastname: Kavanagh
authors.forename: Nadim J
authors.initials: NJ
authors.lastname: Ajami
authors.forename: Elly
authors.initials: E
authors.lastname: Cheng
authors.forename: Max
authors.initials: M
authors.lastname: Ciarlet
authors.forename: Roberto A
authors.initials: RA
authors.lastname: Guerrero
authors.forename: Carl Q-Y
authors.initials: CQ
authors.lastname: Zeng
authors.forename: Sue E
authors.initials: SE
authors.lastname: Crawford
authors.forename: Mary K
authors.initials: MK
authors.lastname: Estes
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000818:Animals; D000906:Antibodies / Q000097:blood; D005260:Female; D006023:Glycoproteins / Q000008:administration & dosage*; D006433:Hemocyanins / Q000276:immunology; D018928:Immunity, Mucosal; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology; D014118:Toxins, Biological / Q000008:administration & dosage*; D014612:Vaccines / Q000008:administration & dosage / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000008:administration & dosage*
chemical_list: D000276:Adjuvants, Immunologic; D000906:Antibodies; D006023:Glycoproteins; C081369:NS28 protein, rotavirus; D013745:Tetanus Toxoid; D014118:Toxins, Biological; D014612:Vaccines; D017361:Viral Nonstructural Proteins; D010047:Ovalbumin; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin