title: Tandem truncated rotavirus VP8* subunit protein with T cell epitope as non-replicating parenteral vaccine is highly immunogenic.
abstract: The two currently available live oral rotavirus vaccines, Rotarix(®) and RotaTeq(®), are highly efficacious in the developed countries. However, the efficacy of such vaccines in resource deprived countries in Africa and Southeast Asia is low. We reported previously that a bacterially-expressed rotavirus P2-P[8] ΔVP8* subunit vaccine candidate administered intramuscularly elicited high-titers of neutralizing antibodies in guinea pigs and mice and significantly shortened the duration of diarrhea in neonatal gnotobiotic pigs upon oral challenge with virulent human rotavirus Wa strain. To further improve its vaccine potential and provide wider coverage against rotavirus strains of global and regional epidemiologic importance, we constructed 2 tandem recombinant VP8* proteins, P2-P[8] ΔVP8*-P[8] ΔVP8* and P2-P[8] ΔVP8*-P[6] ΔVP8* based on Escherichia coli expression system. The two resulting recombinant tandem proteins were highly soluble and P2-P[8] ΔVP8*-P[8] ΔVP8* was generated with high yield. Moreover, guinea pigs immunized intramuscularly by 3 doses of the P2-P[8] ΔVP8*-P[8] ΔVP8* or P2-P[8] ΔVP8*-P[6] ΔVP8* vaccine with aluminum phosphate adjuvant developed high titers of homotypic and heterotypic neutralizing antibodies against human rotaviruses bearing G1-G4, G8, G9 and G12 with P[8], P[4] or P[6] combination. The results suggest that these 2 subunit vaccines in monovalent or bivalent formulation can provide antigenic coverage to almost all the rotavirus G (VP7) types and major P (VP4) types of global as well as regional epidemiologic importance.
authors.affiliation: a College of Animal Science & Veterinary Medicine; Heilongjiang Bayi Agricultural University ; Daqing , Heilongjiang Province , China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Wen
authors.affiliation: b Department of Biomedical Sciences and Pathobiology ; Virginia-Maryland College of Veterinary Medicine; Virginia Polytechnic Institute and State University ; Blacksburg , VA USA.
authors.forename: Dianjun
authors.initials: D
authors.lastname: Cao
authors.affiliation: c Rotavirus Vaccine Development Section; Laboratory of Infectious Diseases; National Institute of Allergy and Infectious Diseases; National Institutes of Health ; Bethesda , MD USA.
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Jones
authors.affiliation: c Rotavirus Vaccine Development Section; Laboratory of Infectious Diseases; National Institute of Allergy and Infectious Diseases; National Institutes of Health ; Bethesda , MD USA.
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Hoshino
authors.affiliation: b Department of Biomedical Sciences and Pathobiology ; Virginia-Maryland College of Veterinary Medicine; Virginia Polytechnic Institute and State University ; Blacksburg , VA USA.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Yuan
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D017607:Aluminum Compounds / Q000008:administration & dosage; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006168:Guinea Pigs; D007273:Injections, Intramuscular; D050505:Mutant Proteins / Q000235:genetics / Q000276:immunology; D010710:Phosphates / Q000008:administration & dosage; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D022243:Rotavirus Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D017607:Aluminum Compounds; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D018984:Epitopes, T-Lymphocyte; D050505:Mutant Proteins; D010710:Phosphates; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D022243:Rotavirus Vaccines; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D017361:Viral Nonstructural Proteins; C079234:NS35 protein, rotavirus; C012714:aluminum phosphate
keywords: P type; VP8* protein; rotavirus; subunit vaccine; universal T cell epitope