Immunogenicity, protective efficacy and safety of a recombinant DNA vaccine encoding truncated Plasmodium yoelii sporozoite asparagine-rich protein 1 (PySAP1)

Hum Vaccin Immunother. 2013 May;9(5):1104-11. doi: 10.4161/hv.23688. Epub 2013 Jan 28.

Abstract

Although great efforts have been undertaken for the development of malaria vaccines, no completely effective malaria vaccines are available yet. Despite being clinically silent, the pre-erythrocytic stage is considered an ideal target for the development of malaria vaccines. Sporozoite asparagine-rich protein 1 (SAP1) is a sporozoite-localized protein that regulates the expression of UIS (upregulated in infectious sporozoites) genes, which are essential for the infectivity of sporozoites. In this study, a recombinant DNA vaccine encoding a predicted antigenic determinant region of Plasmodium yoelii SAP1 (PySAP1) was constructed. Immunization of mice with this DNA vaccine construct resulted in significant elevation of cytokines such as IFN-γ, IL-2, IL-4 and IL-10, and total IgG as compared with control groups immunized with either the empty DNA vector or saline. After challenge with sporozoites, the group receiving the DNA vaccine showed delayed development of parasitemia and prolonged survival time compared with the control group. The DNA vaccine provided partial protection against P. yoelii 17XL infection, with an overall protection rate of 20%. In addition, the DNA vaccine did not show integration into the host genome. Further studies of SAP1 are needed to test whether it can be used as subunit vaccine candidate.

Keywords: DNA vaccine; Plasmodium yoelii17XL; SAP1; malaria vaccine; pre-erythrocytic stage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Protozoan / blood
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Immunoglobulin G / blood
  • Malaria / prevention & control
  • Malaria Vaccines / administration & dosage
  • Malaria Vaccines / adverse effects*
  • Malaria Vaccines / genetics
  • Malaria Vaccines / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Parasitemia / prevention & control
  • Protozoan Proteins / genetics
  • Protozoan Proteins / immunology*
  • Survival Analysis
  • T-Lymphocytes / immunology
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / adverse effects*
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology*
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / adverse effects
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology

Substances

  • Antibodies, Protozoan
  • Cytokines
  • Immunoglobulin G
  • Malaria Vaccines
  • Protozoan Proteins
  • SAP1 protein, Plasmodium yoelii
  • Vaccines, DNA
  • Vaccines, Synthetic