A baculovirus dual expression system-based malaria vaccine induces strong protection against Plasmodium berghei sporozoite challenge in mice

Infect Immun. 2009 May;77(5):1782-9. doi: 10.1128/IAI.01226-08. Epub 2009 Feb 17.

Abstract

We have previously shown that a recombinant baculovirus that displays Plasmodium berghei circumsporozoite protein (PbCSP), a homolog of the leading human malaria vaccine candidate, on the viral envelope protected 60% of mice against P. berghei infection. Here, we describe a second-generation baculovirus vaccine based on the "baculovirus dual expression system," which drives PbCSP expression by a dual promoter that consists of tandemly arranged baculovirus-derived polyhedrin and mammal-derived cytomegalovirus promoters. The baculovirus-based PbCSP vaccine not only displayed PbCSP on the viral envelope but also expressed PbCSP upon transduction of mammalian cells. Immunization with the baculovirus-based PbCSP vaccine elicited high PbCSP-specific antibody titers (predominantly immunoglobulin G1 [IgG1] and IgG2a) and PbCSP-specific CD8(+) T-cell responses without extraneous immunological adjuvants in mice, indicating that there was induction of both Th1 and Th2 responses (a mixed Th1/Th2 response). Importantly, upon intramuscular inoculation, the baculovirus-based PbCSP vaccine conferred complete protection against sporozoite challenge. Thus, the baculovirus-based PbCSP vaccine induced strong protective immune responses against preerythrocytic parasites. These results introduce a novel concept for the baculovirus dual expression system that functions as both a subunit vaccine and a DNA vaccine and offer a promising new alternative to current human vaccine delivery platforms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • Antibodies, Protozoan / blood
  • Baculoviridae / genetics*
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Line
  • Female
  • Genetic Vectors*
  • Humans
  • Immunoglobulin G / blood
  • Interferon-gamma / metabolism
  • Malaria / prevention & control*
  • Malaria Vaccines / genetics*
  • Malaria Vaccines / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Plasmodium berghei / genetics*
  • Plasmodium berghei / immunology*
  • Protozoan Proteins / genetics
  • Protozoan Proteins / immunology
  • Spodoptera
  • Sporozoites / immunology

Substances

  • Antibodies, Protozoan
  • Immunoglobulin G
  • Malaria Vaccines
  • Protozoan Proteins
  • circumsporozoite protein, Protozoan
  • Interferon-gamma