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

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 OD 2.55), IgG2b (mean OD 1.68), and IgG2c (mean OD 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.

Current Strategies to Improve Efficiency of Recombinant Subunit Vaccines

“…In another study, a subunit malaria vaccine against Plasmodium vivax was developed by expressing proteins in E. coli, and the produced protein was delivered in three adjuvants: naloxone, CpG oligodeoxynucleotides, and 3-O-deacylated monophosphoryl lipid A, individually and in combination. The combination of three adjuvants led to an increase in the antibody levels and an enhancement of retention time [40]. These outcomes were supported by similar studies, and the combination of adjuvants holds great promise for improving recombinant subunit vaccines [41].…”

Plasmodium vivax vaccine: What is the best way to go?

“…Recombinant PvTRAP associated with three different adjuvants, NLX, CpG-ODN and 2-O-deacylated monophosphoryl lipid A (MPL), was inoculated individually or mixed and compared with CFA/IFA in mice ( 99 ). After immunization, an increase in the antibody response, especially IgG2b and IgG2c, was observed in all formulations compared to rPvTRAP alone ( 99 ).…”

“…Recombinant PvTRAP associated with three different adjuvants, NLX, CpG-ODN and 2-O-deacylated monophosphoryl lipid A (MPL), was inoculated individually or mixed and compared with CFA/IFA in mice ( 99 ). After immunization, an increase in the antibody response, especially IgG2b and IgG2c, was observed in all formulations compared to rPvTRAP alone ( 99 ). Even though all groups immunized with PvTRAP plus an adjuvant had an increase in IgG2b, IgG2c and IFN-γ, the group that received the mix of adjuvants had the highest levels of those as well as antibodies with greater avidity, which were persistent up to 180 days ( 99 ).…”

“…After immunization, an increase in the antibody response, especially IgG2b and IgG2c, was observed in all formulations compared to rPvTRAP alone ( 99 ). Even though all groups immunized with PvTRAP plus an adjuvant had an increase in IgG2b, IgG2c and IFN-γ, the group that received the mix of adjuvants had the highest levels of those as well as antibodies with greater avidity, which were persistent up to 180 days ( 99 ). In contrast, low levels of IL-10 and no production of IL-4 were detected in any group.…”

“…In contrast, low levels of IL-10 and no production of IL-4 were detected in any group. These results indicate a Th1 response, which is important to eliminate intracellular parasites at the P. vivax liver stage; however, it is still necessary to test the efficacy of this vaccine in challenge models ( 99 ).…”