Protective efficacy of baculovirus dual expression system vaccine expressing Plasmodium falciparum circumsporozoite protein

PLoS One. 2013 Aug 12;8(8):e70819. doi: 10.1371/journal.pone.0070819. eCollection 2013.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology
  • Antibodies, Protozoan / blood
  • Antibodies, Protozoan / immunology
  • Antibody Formation / immunology
  • Antigens, Protozoan / genetics
  • Antigens, Protozoan / immunology*
  • Baculoviridae / genetics*
  • Baculoviridae / immunology
  • Cell Line
  • Disease Models, Animal
  • Gene Expression
  • Gene Order
  • Genetic Vectors / genetics
  • Genetic Vectors / immunology
  • Humans
  • Macaca mulatta
  • Malaria Vaccines / genetics
  • Malaria Vaccines / immunology*
  • Malaria, Falciparum / prevention & control*
  • Mice
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / immunology*
  • Protozoan Proteins / genetics
  • Protozoan Proteins / immunology*
  • T-Lymphocytes / immunology
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology

Substances

  • Antibodies, Neutralizing
  • Antibodies, Protozoan
  • Antigens, Protozoan
  • Malaria Vaccines
  • Protozoan Proteins
  • Vaccines, DNA

Grants and funding

This work was supported in part from a Grant-in-Aid for Young Scientists from the Hokuriku Bank, Ltd.,(http://www.hokuhoku-fg.co.jp/english/) and Grants-in-Aid for Scientific Research (B) (JSPS KAKENHI Grant Number 21390126) (http://www.jsps.go.jp/english/e-grants/index.html), grants from the Waksman Foundation (http://www.waksman.or.jp/) and Otsuka Pharmaceutical Co. Ltd. (http://www.otsuka.co.jp/en/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.