TH1 IMMUNE RESPONSES CONFERRED BY MIXTURE OF NALOXONE, CPG OLIGODEOXYNUCLEOTIDE AND 3-O-DECYLATED MONOPHOSPHORYL LIPID A, AGAINST PLASMODIUM VIVAX RECOMBINANT TRAP AS A SUBUNIT VACCINE IN MOUSE MODEL

Background and Aim:A key tool for the control, elimination, and eradication of Plasmodium vivax is the development of an effective vaccine; however, there is no available effective vaccine against P. vivax. The thrombospondin-related adhesion protein (TRAP) is one of the major sporozoite antigens that plays an important role in the invasion of hepatocytes by sporozoites and it is a promising malaria vaccine candidate. The goal of this study was to investigate the role of antibodies and cellular immune responses induced by purified recombinant PvTRAP delivered in mixture of three adjuvants, naloxone (NLX), CpG oligodeoxy nucleotides ODN 1826 (CpG ODN) and 3-O-decylated monophosphoryl lipid A (MPL), was evaluated in immunized C57BL/6 mice.Methods:For this purpose, the rPvTRAP alone or combined with a mixture of NLX-MPL-CpG adjuvants and Freund s Complete Adjuvant (CFA) were applied for immunization of mice. Antibody-dependent immune mechanisms (IgG, IgG1, IgG2b, IgG2c, and IgG3 responses) as well as the IFN-γ, IL-4, and IL-10 cytokines were determined in post-immunized mouse plasma.Results:The highest level of anti-rPvTRAP 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. Also, mice receiving rPvTRAP/NLX-MPL-CpG induced significantly the higher levels of interferon gamma (IFN-γ) (P < 0.05, independent sample t-test), low level of detectable IL-10, and no detectable IL-4 production.Conclusion:In general, the results exhibited that rPvTRAP is immunogenic and its administration with mixture of CPG-MPL-NLX in mice induced Th1 immune response and had more potential to increase the level and persistence of anti-TRAP antibodies.

Keywords:

Plasmodium vivax , TRAP , MPL , CpG , NLX , Vaccine