Adjuvant effect of Ubenimex on a DNA vaccine for HIV‐1

Enhancement of DNA vaccine immunogenicity is a current topic of high priority in the field of applied immunology, especially as a means of controlling HIV infection. The adjuvant effect of Ubenimex (UBX), an anti‐cancer immunomodulator, on a DNA AIDS vaccine which we developed was examined in a murine model. UBX was formulated into a preparation containing DNA plasmids encoding env and rev genes of HIV‐1 strain III B , and was inoculated intramuscularly into BALB/c mice. The sera obtained with this mixture had 2 3 –2 5 times higher specific IgG titres than those obtained without the use of the adjuvant. UBX also elicited both a stronger HIV‐1‐specific DTH reaction, as measured by the footpad swelling test, and stronger cytotoxic T lymphocyte activity, as assayed by the 51 Cr‐release method, compared with responses using DNA alone. The cytokine secretion profile of restimulated immune lymphoid cells showed that UBX raised IL‐2 and interferon‐gamma levels and decreased IL‐4 production. HIV‐1‐specific immunoglobulin subtype analysis demonstrated that UBX stimulated IgG2a production but suppressed synthesis of IgG1 and IgE. These results indicate that activation of the T‐helper type 1 subset was induced by UBX, suggesting a mechanism of immunomodulation mediated by this agent. We conclude that UBX acts as an immunologic adjuvant for DNA vaccination against HIV‐1. UBX may be a suitable adjuvant for clinical use because of its lack of antigenicity and low toxicity.