title: Construction and characterization of human rotavirus recombinant VP8* subunit parenteral vaccine candidates.
abstract: Two currently licensed live oral rotavirus vaccines (Rotarix® and RotaTeq®) are highly efficacious against severe rotavirus diarrhea. However, the efficacy of such vaccines in selected low-income African and Asian countries is much lower than that in middle or high-income countries. Additionally, these two vaccines have recently been associated with rare case of intussusception in vaccinated infants. We developed a novel recombinant subunit parenteral rotavirus vaccine which may be more effective in low-income countries and also avert the potential problem of intussusception. Truncated recombinant VP8* (ΔVP8*) protein of human rotavirus strain Wa P[8], DS-1 P[4] or 1076 P[6] expressed in Escherichia coli was highly soluble and was generated in high yield. Guinea pigs hyperimmunized intramuscularly with each of the ΔVP8* proteins (i.e., P[8], P[4] or P[6]) developed high levels of homotypic as well as variable levels of heterotypic neutralizing antibodies. Moreover, the selected ΔVP8* proteins when administered to mice at a clinically relevant dosage, route and schedule, elicited high levels of serum anti-VP8* IgG and/or neutralizing antibodies. Our data indicated that the ΔVP8* proteins may be a plausible additional candidate as new parenteral rotavirus vaccines.
authors.affiliation: Rotavirus Vaccine Development Section, Laboratory of Infectious Diseases, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Wen
authors.forename: Dianjun
authors.initials: D
authors.lastname: Cao
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Jones
authors.forename: Jianping
authors.initials: J
authors.lastname: Li
authors.forename: Shousun
authors.initials: S
authors.lastname: Szu
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Hoshino
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D002522:Chlorocebus aethiops; D004926:Escherichia coli; D005260:Female; D006168:Guinea Pigs; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D010957:Plasmids; D016601:RNA-Binding Proteins / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D012401:Rotavirus / Q000276:immunology; D012400:Rotavirus Infections / Q000517:prevention & control*; D022243:Rotavirus Vaccines / Q000096:biosynthesis / Q000276:immunology*; D022223:Vaccines, Subunit / Q000096:biosynthesis / Q000276:immunology; D014614:Vaccines, Synthetic / Q000096:biosynthesis / Q000276:immunology; D014709:Vero Cells; D017361:Viral Nonstructural Proteins / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007074:Immunoglobulin G; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D022243:Rotavirus Vaccines; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D017361:Viral Nonstructural Proteins; C079234:NS35 protein, rotavirus