Baculovirus virions displaying Plasmodium berghei circumsporozoite protein protect mice against malaria sporozoite infection

Virology. 2003 Nov 10;316(1):161-70. doi: 10.1016/j.virol.2003.08.003.

Abstract

The display of foreign proteins on the surface of baculovirus virions has provided a tool for the analysis of protein-protein interactions and for cell-specific targeting in gene transfer applications. To evaluate the baculovirus display system as a vaccine vehicle, we have generated a recombinant baculovirus (AcNPV-CSPsurf) that displays rodent malaria Plasmodium berghei circumsporozoite protein (PbCSP) on the virion surface as a fusion protein with the major baculovirus envelope glycoprotein gp64. The PbCSP-gp64 fusion protein was incorporated and oligomerized on the virion surface and led to a 12-fold increase in the binding activity of AcNPV-CSPsurf virions to HepG2 cells. Immunization with adjuvant-free AcNPV-CSPsurf virions induced high levels of antibodies and gamma interferon-secreting cells against PbCSP and protected 60% of mice against sporozoite challenge. These data demonstrate that AcNPV-CSPsurf displays sporozoite-like PbCSP on the virion surface and possesses dual potentials as a malaria vaccine candidate and a liver-directed gene delivery vehicle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Protozoan / blood
  • Baculoviridae / genetics*
  • Baculoviridae / immunology
  • Baculoviridae / metabolism
  • Cell Line
  • Genetic Vectors
  • Humans
  • Immunization
  • Malaria / parasitology
  • Malaria / prevention & control*
  • Malaria Vaccines* / administration & dosage
  • Malaria Vaccines* / genetics
  • Malaria Vaccines* / immunology
  • Mice
  • Mice, Inbred BALB C
  • Plasmodium berghei / growth & development
  • Plasmodium berghei / immunology*
  • Plasmodium berghei / pathogenicity
  • Protozoan Proteins / genetics
  • Protozoan Proteins / immunology
  • Protozoan Proteins / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Sporozoites / pathogenicity
  • Viral Fusion Proteins / genetics
  • Viral Fusion Proteins / immunology
  • Viral Fusion Proteins / metabolism
  • Virion / genetics*
  • Virion / immunology
  • Virion / metabolism

Substances

  • Antibodies, Protozoan
  • Malaria Vaccines
  • Protozoan Proteins
  • Recombinant Fusion Proteins
  • Viral Fusion Proteins
  • circumsporozoite protein, Protozoan