Vaccine adjuvants CpG (oligodeoxynucleotides ODNs), MPL (3-O-deacylated monophosphoryl lipid A) and naloxone-enhanced Th1 immune response to the Plasmodium vivax recombinant thrombospondin-related adhesive protein (TRAP) in mice

Med Microbiol Immunol. 2018 Nov;207(5-6):271-286. doi: 10.1007/s00430-018-0545-2. Epub 2018 Jun 9.

Abstract

Despite considerable efforts toward vaccine development over decades, there is no available effective vaccine against Plasmodium vivax. Thrombospondin-related adhesive protein of P. vivax (PvTRAP) is essential for sporozoite motility and invasions into mosquito's salivary gland and vertebrate's hepatocyte; hence, it is a promising target for pre-erythrocytic vaccine. In the current investigation, the role of antibodies and cellular immune responses induced by purified recombinant PvTRAP (rPvTRAP) delivered in three adjuvants, naloxone (NLX), CpG oligodeoxynucleotides ODN1826 (CpG-ODN), and 3-O-deacylated monophosphoryl lipid A (MPL), alone and in combination was evaluated in immunized C57BL/6 mice. The highest level and the avidity of anti-PvTRAP IgG (mean OD490nm 2.55), IgG2b (mean OD490nm 1.68), and IgG2c (mean OD490nm 1.466) were identified in the group received rPvTRA/NLX-MPL-CpG. This group also presented the highest IgG2c/IgG1 (2.58) and IgG2b/IgG1 (2.95) ratio when compared to all other groups, and among the adjuvant groups, the lowest IgG2c/IgG1 (1.86) and IgG2b/IgG1 (2.25) ratio was observed in mice receiving rPvTRAP/NLX. Mice receiving rPvTRAP/adjuvants induced significantly the higher levels of interferon gamma (IFN-γ), low level of detectable IL-10, and no detectable IL-4 production. The present result revealed that PvTRAP is immunogenic and its administration with CPG, MPL, and NLX in C57BL/6 mice induced Th1 immune response. Besides, the rPvTRAP delivery in the mixed formulation of those adjuvants had more potential to increase the level, avidity, and persistence of anti-TRAP antibodies. However, it warrants further assessment to test the blocking activity of the produced antibodies in immunized mice with different adjuvant formulations.

Keywords: Adjuvant; Malaria; Plasmodium vivax; TRAP; Vaccine.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Animals
  • Antibodies, Protozoan / blood
  • Female
  • Immunoglobulin G / blood
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-4 / metabolism
  • Leukocytes, Mononuclear / immunology
  • Lipid A / administration & dosage
  • Lipid A / analogs & derivatives*
  • Malaria Vaccines / administration & dosage
  • Malaria Vaccines / genetics
  • Malaria Vaccines / immunology*
  • Mice, Inbred C57BL
  • Naloxone / administration & dosage*
  • Oligodeoxyribonucleotides / administration & dosage*
  • Plasmodium vivax / immunology
  • Protozoan Proteins / genetics
  • Protozoan Proteins / immunology*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Th1 Cells / immunology*
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology

Substances

  • Adjuvants, Immunologic
  • Antibodies, Protozoan
  • CPG-oligonucleotide
  • Immunoglobulin G
  • Lipid A
  • Malaria Vaccines
  • Oligodeoxyribonucleotides
  • Protozoan Proteins
  • Recombinant Proteins
  • Vaccines, Synthetic
  • thrombospondin-related adhesive protein, protozoan
  • Interleukin-10
  • Interleukin-4
  • Naloxone
  • Interferon-gamma
  • monophosphoryl lipid A