Administration of naloxone in combination with recombinant Plasmodium vivax AMA‐1 in BALB/c mice induces mixed Th1/Th2 immune responses

Abstract

Naloxone (NLX) has the ability to shift the immune response to a Th1 profile. Therefore, the adjuvant efficacy of NLX with recombinant P. vivax apical membrane antigen-1(rPvAMA-1) in BALB/c mice was evaluated. Mice were immunized subcutaneously with purified rPvAMA-1 formulated with NLX (doses of 5 mg/kg body weight) alone or in combination with IFA. A significant increase in anti-PvAMA-1 IgG antibody after the second boost (mean OD = 2·08 and 2·17, in groups received, rPvAMA-1/NLX and rPvAMA-1/NLX/IFA, respectively) was detected. IgG1 and IgG2b were the predominant isotypes in all immunized mouse groups. In immunized mice with rPvAMA-1/NLX (mean: 1036 pg/mL) and with rPvAMA-1/NLX/IFA (mean: 1024 pg/mL), IFN-γ was elicited in response to rPvAMA-1 after the second boost. No detectable IL-4 secretion was determined in all tested groups. In conclusion, the administration of NLX alone or NLX/IFA with rPvAMA-1 in BALB/c mice, which induced mixed Th1/Th2 immune responses, was comparable with that of the same recombinant antigen with CFA/IFA adjuvant. The results indicate that NLX alone may possibly not be considered as a potent Th1 adjuvant in PvAMA-1-based vaccine. However, in order to modulate immune responses from mixed Th1/Th2 to strong and protective Th1 response, further study is warranted on combination of NLX with other adjuvants such as CpG motifs or MPL in proper vaccine formulation. Additionally, dose-response study is necessary to determine the effect of different doses of antigen combined with NLX (at various doses) in Balb/c mice.

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

“…Therefore, it can generally be concluded that for shifting immune responses to strong and specific Th1 response to PvTRAP, adjuvants MPL, CpG, and to a lesser extent, to NLX are suitable. Interestingly, this finding is in contrast to a previous work [56] in which NLX together with rPvAMA-1 could induce mixed Th1/Th2 responses; however, this adjuvant with rPvTRAP produced more Th1 than Th2 responses, suggesting a role for the nature of antigen in the immune responses. The immune sera from mice vaccinated with the rPvTRAP/adjuvants groups exhibited IgG antibody with the high avidity on days 38 and 180 of first immunization, which is likely due to the maturation of immune response and the selection of clonal B-cells that result in IgG avidity increases [65].…”

“…Immunized mouse sera were evaluated for anti-rPvTRAPspecific antibodies by ELISA as described previously [56] with some modifications. Briefly, rPvTRAP protein (50 ng/ well) was diluted in a coating buffer (0.06 M Na 2 CO 3 / NaHCO 3 , pH 9.6), coated in Maxisorp flat-bottom 96-well ELISA plates (Jet Biofil) and kept at 4 °C overnight.…”

A multi-epitope vaccine GILE against Echinococcus Multilocularis infection in mice

“…Both Th1 and Th2 cells can express the β1 chain of the IL-12 receptor, but only Th1 cells can express the β2 chain. Th2 cells without β2 chain could not be directly transformed into Th1 cells ( 36 ), but Th1 cells could be transformed into Th2 cells ( 37 ). These results indicate that the shift from Th1 to Th2 induced by E. Multilocularis infection would cause immunosuppression of the host and thus allow E. Multilocularis to escape from the immune system and continue to grow.…”

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

“…Antibodies against PvAMA-1 have an invasion inhibitory role against diverse P. vivax strains (212). Someabozorg et al (213) demonstrated that naloxone (NLX) alone as an adjuvant in a vaccine formulation with recombinant PvAMA-1 cannot induce a good immune response. However, in combination with another adjuvant, such as IFA, a balanced Th1/Th2 response was obtained (213).…”