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A Baculovirus Dual Expression System-Based Malaria Vaccine Induces Strong Protection against Plasmodium berghei Sporozoite Challenge in Mice

Yoshida, Shigeto, Kawasaki, Masanori, Hariguchi, Norimitsu, Hirota, Kuniko, Matsumoto, Makoto
Infection and immunity 2009 v.77 no.5 pp. 1782-1789
Baculoviridae, Plasmodium berghei, adjuvants, genetic vectors, humans, immune response, immunization, immunoglobulins, malaria, mice, parasites, protozoan vaccines, recombinant vaccines
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.