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

摘要

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 5mg/kg body weight) alone or in combination with IFA. A significant increase in anti-PvAMA-1 IgG antibody after the second boost (mean OD490=208 and 217, 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: 1036pg/mL) and with rPvAMA-1/NLX/IFA (mean: 1024pg/mL), IFN- 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.