Affinity-purified dengue-2 virus envelope glycoprotein induces neutralizing antibodies and protective immunity in mice

Vaccine. 1997 Dec;15(17-18):1946-54. doi: 10.1016/s0264-410x(97)00128-x.

Abstract

We constructed a recombinant baculovirus which produces a dengue (DEN)-2 virus envelope (E) protein containing a six-histidine (H6) tag in place of the last 100 amino acids at its C-terminus. The recombinant protein was purified from the supernatant of baculovirus-infected Spodoptera frugiperda insect cell cultures to apparent homogeneity by cation-chelation chromatography (TALON) in which the H6-tagged E-protein was eluted under non-denaturing conditions with 100 mM imidazole at pH 8.0. Mice vaccinated with the purified E mixed with aluminium hydroxide adjuvant showed an immune response of IgM and IgG1, IgG2a and IgG2b isotypes, and neutralizing antibodies, similar to that following immunization with purified inactivated DEN-2 virus. Moreover, mice that received the purified recombinant protein were significantly protected against 200 50% lethal dose of DEN-2 virus. This combination of affinity purified H6-tagged protein and adsorption onto a cationic carrier seems promising for the production of immunogenic particulate proteins, especially DEN protein for the four serotypes, and the development of a new generation of vaccines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / biosynthesis*
  • Baculoviridae / genetics
  • Baculoviridae / metabolism
  • Chlorocebus aethiops
  • Chromatography, Affinity
  • Dimerization
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neutralization Tests
  • Recombinant Proteins / immunology
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / therapeutic use
  • Severe Dengue / immunology
  • Severe Dengue / prevention & control*
  • Spodoptera / virology
  • Vero Cells
  • Viral Envelope Proteins / immunology*
  • Viral Envelope Proteins / isolation & purification
  • Viral Envelope Proteins / therapeutic use*

Substances

  • Antibodies, Viral
  • E-glycoprotein, Dengue virus type 2
  • Recombinant Proteins
  • Viral Envelope Proteins