Medical Microbiology and Immunology

, Volume 207, Issue 5–6, pp 271–286 | Cite as

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

  • Saeed Nazeri
  • Sedigheh ZakeriEmail author
  • Akram A. Mehrizi
  • Navid D. Djadid
  • Georges Snounou
  • Chiara Andolina
  • François Nosten
Original Investigation


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.


Malaria Plasmodium vivax Vaccine TRAP Adjuvant 



We would like to thank Dr. Amir Amanzadeh for his technical advice in HepG2 culturing. This study was funded by a grant (No. 747) from Pasteur Institute of Iran to S. Zakeri and also by Ph.D. scholarship to S. Nazeri.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All animal handling was in accordance with the ethical standards of the Laboratory Animal Science Department, Pasteur Institute of Iran.

Supplementary material

430_2018_545_MOESM1_ESM.docx (14 kb)
Supplementary material 1 (DOCX 13 KB)
430_2018_545_MOESM2_ESM.docx (15 kb)
Supplementary material 2 (DOCX 15 KB)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Malaria and Vector Research Group (MVRG), Biotechnology Research Center (BRC)Pasteur Institute of IranTehranIran
  2. 2.Sorbonne Universités, UPMC Univ Paris 06, Inserm (Institut National de la Santé et de la Recherche Medicale), Centre d’Immunologie et des Maladies Infectieuses (Cimi-Paris), UMR 1135, ERL CNRS 8255 (Centre National de la Recherche Scientifique)ParisFrance
  3. 3.Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical MedicineMahidol UniversityMae SotThailand
  4. 4.Centre for Tropical Medicine and Global Health, Nuffield Department of MedicineUniversity of OxfordOxfordUK

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