Construction and characterization of human rotavirus recombinant VP8* subunit parenteral vaccine candidates

Vaccine. 2012 Sep 21;30(43):6121-6. doi: 10.1016/j.vaccine.2012.07.078. Epub 2012 Aug 9.

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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Chlorocebus aethiops
  • Escherichia coli
  • Female
  • Guinea Pigs
  • Immunoglobulin G / blood
  • Mice
  • Plasmids
  • RNA-Binding Proteins / immunology*
  • Recombinant Proteins / immunology
  • Rotavirus / immunology
  • Rotavirus Infections / prevention & control*
  • Rotavirus Vaccines / biosynthesis
  • Rotavirus Vaccines / immunology*
  • Vaccines, Subunit / biosynthesis
  • Vaccines, Subunit / immunology
  • Vaccines, Synthetic / biosynthesis
  • Vaccines, Synthetic / immunology
  • Vero Cells
  • Viral Nonstructural Proteins / immunology*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Immunoglobulin G
  • RNA-Binding Proteins
  • Recombinant Proteins
  • Rotavirus Vaccines
  • Vaccines, Subunit
  • Vaccines, Synthetic
  • Viral Nonstructural Proteins
  • NS35 protein, rotavirus