Preclinical vaccine study of Plasmodium vivax circumsporozoite protein derived-synthetic polypeptides formulated in montanide ISA 720 and montanide ISA 51 adjuvants

Am J Trop Med Hyg. 2011 Feb;84(2 Suppl):21-7. doi: 10.4269/ajtmh.2011.10-0110.

Abstract

Plasmodium vivax circumsporozoite (CS) protein is a leading malaria vaccine candidate previously assessed in animals and humans. Here, combinations of three synthetic polypeptides corresponding to amino (N), central repeat (R), and carboxyl (C) regions of the CS protein formulated in Montanide ISA 720 or Montanide ISA 51 adjuvants were assessed for immunogenicity in rodents and primates. BALB/c mice and Aotus monkeys were divided into test and control groups and were immunized three times with doses of 50 and 100 μg of vaccine or placebo. Antigen-specific antimalarial antibodies were determined by enzyme-linked immunosorbent assay, immunofluorescent antibody test, and IFN-γ responses by enzyme-linked immunosorbent spot (ELIspot). Both vaccine formulations were highly immunogenic in both species. Mice developed better antibody responses against C and R polypeptides, whereas the N polypeptide was more immunogenic in monkeys. Anti-peptide antibodies remained detectable for several months and recognized native proteins on sporozoites. Differences between Montanide ISA 720 and Montanide ISA 51 formulations were not significant.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Animals
  • Antibodies, Protozoan / blood
  • Aotidae
  • Dose-Response Relationship, Immunologic
  • Drug Evaluation, Preclinical
  • Interferon-gamma / metabolism
  • Leukocytes, Mononuclear / metabolism
  • Malaria Vaccines / immunology*
  • Mannitol / administration & dosage
  • Mannitol / analogs & derivatives*
  • Mice
  • Mice, Inbred BALB C
  • Oleic Acids / administration & dosage*
  • Plasmodium vivax / immunology*
  • Protozoan Proteins / chemistry
  • Protozoan Proteins / immunology*

Substances

  • Adjuvants, Immunologic
  • Antibodies, Protozoan
  • Malaria Vaccines
  • Oleic Acids
  • Protozoan Proteins
  • circumsporozoite protein, Protozoan
  • montanide ISA 51
  • mannide monooleate
  • Mannitol
  • Interferon-gamma