title: Baculovirus-based vaccination vectors allow for efficient induction of immune responses against plasmodium falciparum circumsporozoite protein.
abstract: Baculovirus vectors are able to transduce a large variety of mammalian cell types and express transgenes placed under the control of heterologous promoters. In this study, we evaluated the potential of baculovirus vectors for malaria vaccination. To induce efficient CD4(+) and CD8(+) T-cell responses, we produced a series of vectors that display the Plasmodium falciparum circumsporozoite (CS) protein in the virion envelope and/or allow for CS expression upon transduction of mammalian cells. We found that baculovirus vectors can transduce professional antigen-presenting cells and trigger their maturation, which is a prerequisite for efficient antigen presentation. Upon intramuscular injection into mice, the vector that both displayed and expressed CS induced higher anti-CS antibody titers (of the immunoglobulin (IgG)1 and IgG2a type) and a higher frequency of interferon-gamma-producing T cells specific to CS, than the vectors which either only displayed or only expressed CS. The baculovirus CS display/expression vector was also superior in inducing CS-specific CD4(+) and CD8(+) T-cell responses in vitro using human peripheral blood mononuclear cells from naive donors. This, together with the absence of pre-existing immunity to baculoviruses in humans, the absence of viral gene expression in mammalian cells, and the relative low immunogenicity of baculovirus virions, makes these vectors promising tools for vaccination. Furthermore, the ability to produce large amounts in serum-free medium at a low cost adds a further advantage to this vector system.
authors.affiliation: Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Strauss
authors.forename: Andreas
authors.initials: A
authors.lastname: Hüser
authors.forename: Shaoheng
authors.initials: S
authors.lastname: Ni
authors.forename: Sebastian
authors.initials: S
authors.lastname: Tuve
authors.forename: Nancy
authors.initials: N
authors.lastname: Kiviat
authors.forename: Papa Salif
authors.initials: PS
authors.lastname: Sow
authors.forename: Christian
authors.initials: C
authors.lastname: Hofmann
authors.forename: André
authors.initials: A
authors.lastname: Lieber
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D016367:Baculoviridae / Q000235:genetics* / Q000276:immunology*; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018411:Spodoptera; D014611:Vaccination
chemical_list: D000913:Antibodies, Protozoan; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan