Protective efficacy of baculovirus dual expression system vaccine expressing Plasmodium falciparum circumsporozoite protein.
We have previously developed a new malaria vaccine delivery system based on the baculovirus dual expression system (BDES). In this system, expression of malaria antigens is driven by a dual promoter consisting of the baculovirus-derived polyhedrin and mammal-derived cytomegalovirus promoters. To test this system for its potential as a vaccine against human malaria parasites, we investigated immune responses against the newly developed BDES-based Plasmodium falciparum circumsporozoite protein vaccines (BDES-PfCSP) in mice and Rhesus monkeys. Immunization of mice with BDES-PfCSP induced Th1/Th2-mixed type immune responses with high PfCSP-specific antibody (Ab) titers, and provided significant protection against challenge from the bites of mosquitoes infected with a transgenic P. berghei line expressing PfCSP. Next, we evaluated the immunogenicity of the BDES-PfCSP vaccine in a rhesus monkey model. Immunization of BDES-PfCSP elicited high levels of anti-PfCSP Ab responses in individual monkeys. Moreover, the sera from the immunized monkeys remarkably blocked sporozoite invasion of HepG2 cells. Taken together with two animal models, our results indicate that this novel vaccine platform (BDES) has potential clinical application as a vaccine against malaria.
Laboratory of Vaccinology and Applied Immunology, Kanazawa University School of Pharmacy, Kanazawa, Japan.
Mitsuhiro
M
Iyori
Hiroki
H
Nakaya
Katsuya
K
Inagaki
Sathit
S
Pichyangkul
Daisuke S
DS
Yamamoto
Masanori
M
Kawasaki
Kyungtak
K
Kwak
Masami
M
Mizukoshi
Yoshihiro
Y
Goto
Hiroyuki
H
Matsuoka
Makoto
M
Matsumoto
Shigeto
S
Yoshida
D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D016367:Baculoviridae / Q000235:genetics* / Q000276:immunology; D002460:Cell Line; D004195:Disease Models, Animal; D015870:Gene Expression; D023061:Gene Order; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D006801:Humans; D008253:Macaca mulatta; D017780:Malaria Vaccines / Q000235:genetics / Q000276:immunology*; D016778:Malaria, Falciparum / Q000517:prevention & control*; D051379:Mice; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology
D057134:Antibodies, Neutralizing; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D019444:Vaccines, DNA