A baculovirus dual expression system-based malaria vaccine induces strong protection against Plasmodium berghei sporozoite challenge in mice.
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.
Yoshida
Shigeto
S
Division of Medical Zoology, Department of Infection and Immunity, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan. shigeto@jichi.ac.jp
Kawasaki
Masanori
M
Hariguchi
Norimitsu
N
Hirota
Kuniko
K
Matsumoto
Makoto
M
D000281:Administration, Intranasal; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D016367:Baculoviridae / Q000235:genetics*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D008288:Malaria / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010962:Plasmodium berghei / Q000235:genetics* / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D018411:Spodoptera; D034101:Sporozoites / Q000276:immunology
D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan; D007371:Interferon-gamma