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

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

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  • 1Division of Medical Zoology, Department of Infection and Immunity, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan. shigeto@jichi.ac.jp

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.

PMID:
19223476
PMCID:
PMC2681746
DOI:
10.1128/IAI.01226-08
[PubMed - indexed for MEDLINE]
Free PMC Article
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