Abstract
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.
Highlights
Malaria is one of the world’s most devastating infectious diseases and is a major killer of children under five years old in Africa
We have developed a ‘‘baculovirus dual expression system (BDES)’’, which drives malaria antigen expression by a dual promoter that consists of both baculovirus-derived polyhedrin and mammal-derived cytomegalovirus (CMV) promoters [13,14,15,16]
The construct designated ‘‘CMV-full’’ harbored a gene cassette consisting of the gp64 major envelope protein signal sequence and the gene encoding PfCSP19–373 fused to the N-terminus of AcNPV gp64, which was driven by the CMVie/polyhedrin dual promoter
Summary
Malaria is one of the world’s most devastating infectious diseases and is a major killer of children under five years old in Africa. The most advanced malaria vaccine candidate, RTS,S/AS01, a Plasmodium falciparum circumsporozoite protein (PfCSP)-based vaccine containing the specific adjuvant AS01 was developed many years ago [2]. This vaccine is based on an N-terminal truncated form of PfCSP, which is fused to the hepatitis B surface antigen on the virus-like particle (VLP) platform [3,4]. New and more effective vaccine delivery systems are urgently needed for malaria vaccines
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