CpG Oligodeoxynucleotide and Montanide ISA 51 Adjuvant Combination Enhanced the Protective Efficacy of a Subunit Malaria Vaccine

Abstract

Unmethylated CpG dinucleotide motifs present in bacterial genomes or synthetic oligodeoxynucleotides (ODNs) serve as strong immunostimulatory agents in mice, monkeys and humans. We determined the adjuvant effect of murine CpG ODN 1826 on the immunogenicity and protective efficacy of the Saccharomyces cerevisiae-expressed 19-kDa C-terminal region of merozoite surface protein 1 (yMSP1(sub19)) of the murine malaria parasite Plasmodium yoelii. We found that in C57BL/6 mice, following sporozoite challenge, the degree of protective immunity against malaria induced by yMSP1(sub19) in a formulation of Montanide ISA 51 (ISA) plus CpG ODN 1826 was similar or superior to that conferred by yMSP1(sub19) emulsified in complete Freund s adjuvant (CFA/incomplete Freund s adjuvant). In total, among mice immunized with yMSP1(sub19), 22 of 32 (68.7%) with ISA plus CpG 1826, 0 of 4 (0%) with CFA/incomplete Freund s adjuvant, 0 of 4 (0%) with CpG 1826 mixed with ISA (no yMSP1(sub19)), and 0 of 11 (0%) with CpG 1826 alone were completely protected against development of erythrocytic stage infection after sporozoite challenge. The adjuvant effect of CpG ODN 1826 was manifested as both significantly improved complete protection from malaria (defined as the absence of detectable erythrocytic form parasites) (P 0.007, chi square) and reduced parasite burden in infected mice. In vivo depletions of interleukin-12 and gamma interferon cytokines and CD4 and CD8 T cells in vaccinated mice had no significant effect on immunity. On the other hand, immunoglobulin G (IgG) isotype levels appeared to correlate with protection. .

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Document Details

Document Type
Technical Report
Publication Date
Feb 01, 2004
Accession Number
ADA457927

Entities

People

  • Alem Taye
  • Anthony W. Stowers
  • Arthur M. Krieg
  • David C. Kaslow
  • Hong Zheng
  • Miranda S. Oakley
  • Sanjai Kumar
  • Shanmuga P. Kuppusamy
  • Stephen L. Hoffman
  • Trevor R. Jones

Organizations

  • Naval Submarine Medical Research Laboratory

Tags

DTIC Thesaurus Topics

  • Biological Factors
  • Blood
  • Cells
  • Chemistry
  • Freund'S Adjuvant
  • Immunity
  • Immunization
  • Immunogenicity
  • Infection
  • Infectious Diseases
  • Lymphocytes
  • Malaria
  • Materials
  • Parasitic Diseases
  • Proteins
  • Recombinant Proteins
  • Vaccines

Fields of Study

  • Biology

Readers

  • Immunology
  • Molecular Genetics
  • Parasitology and Pharmacology of Malaria.

Technology Areas

  • Biotechnology
  • Biotechnology - Cancer Biotech