Baculovirus virions displaying Plasmodium berghei circumsporozoite protein protect mice against malaria sporozoite infection.
The display of foreign proteins on the surface of baculovirus virions has provided a tool for the analysis of protein-protein interactions and for cell-specific targeting in gene transfer applications. To evaluate the baculovirus display system as a vaccine vehicle, we have generated a recombinant baculovirus (AcNPV-CSPsurf) that displays rodent malaria Plasmodium berghei circumsporozoite protein (PbCSP) on the virion surface as a fusion protein with the major baculovirus envelope glycoprotein gp64. The PbCSP-gp64 fusion protein was incorporated and oligomerized on the virion surface and led to a 12-fold increase in the binding activity of AcNPV-CSPsurf virions to HepG2 cells. Immunization with adjuvant-free AcNPV-CSPsurf virions induced high levels of antibodies and gamma interferon-secreting cells against PbCSP and protected 60% of mice against sporozoite challenge. These data demonstrate that AcNPV-CSPsurf displays sporozoite-like PbCSP on the virion surface and possesses dual potentials as a malaria vaccine candidate and a liver-directed gene delivery vehicle.
Division of Medical Zoology, Department of Infection and Immunity, Jichi Medical School, 329-0498, Tochigi, Japan. shigeto@jichi.ac.jp
Shigeto
S
Yoshida
Daisuke
D
Kondoh
Eriko
E
Arai
Hiroyuki
H
Matsuoka
Chisato
C
Seki
Takao
T
Tanaka
Masaji
M
Okada
Akira
A
Ishii
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D016367:Baculoviridae / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D005822:Genetic Vectors; D006801:Humans; D007114:Immunization; D008288:Malaria / Q000469:parasitology / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010962:Plasmodium berghei / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D034101:Sporozoites / Q000472:pathogenicity; D014760:Viral Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014771:Virion / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; D014760:Viral Fusion Proteins; C041595:circumsporozoite protein, Protozoan