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. 1998 Jan;111(1):30-5.
doi: 10.1046/j.1365-2249.1998.00466.x.

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

S Sasaki  1 , J Fukushima, K Hamajima, N Ishii, T Tsuji, K Q Xin, H Mohri, K Okuda
Affiliations

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

S Sasaki et al. Clin Exp Immunol. 1998 Jan.

Erratum in

  • Clin Exp Immunol 1998 May;112(2):354

Abstract

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 51Cr-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.

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Figures

Fig. 1
Fig. 1
Adjuvant effect of Ubenimex (UBX) on humoral immune responses induced by DNA vaccination. The HIV-1-specific serum IgG titre (a) and IgG1, IgG2a and IgE production (b) are represented in the separate panels. Mice were intramuscularly immunized once with 2mg each of pCMV160IIIB and pcREV (total 4 μg) in a mixture formulated with the indicated doses of UBX. The HIV-1-specific IgG titre was determined in duplicate by ELISA 4 and 8 weeks following immunization. The IgG1, IgG2a and IgE responses were assayed using the 4-week sample. Results are expressed as the means±s.e.m. of four to six mice. *, ** Significant difference between the UBX-formulated and unformulated groups (P <0.05 and P <0.01, respectively). Similar results were obtained in a separate experiment. IIIB/REV, pCMV160IIIB and pcREV; ND, not detected.
Fig. 2
Fig. 2
Cytolytic activity of bulk splenic mononuclear cells from BALB/c mice immunized with 2mg each of pCMV160IIIB and pcREV (total 4μg) in a mixture formulated with the indicated dose of Ubenimex (UBX). Effector spleen cells were cultured with the V3 peptide (CTL epitope of HIV-1IIIB), and syngenic cells (P815; H-2d) pulsed with or without the same peptide were used as targets. Specific cytolytic activity was titrated with an effector-to-target cell (E/T) ratio of as 5, 20 and 80, but antigen-unrestricted cytolysis was assayed at E/T ratio 80 only. Duplicated assays were performed and results are expressed as the means±s.e.m. of three or five mice comprising the control or experimental group, respectively. *, ** Significant differences between the UBX-formulated and unformulated groups (P <0.05 and P <0.01, respectively).
Fig. 3
Fig. 3
Cytokine production by restimulated splenocytes from mice inoculated with the vaccine formulated as shown. (a, b) Th1- (IL-2 and IFN-γ) and Th2-type (IL-4) cytokines, respectively. Mice were treated using the protocols specified in the legend for Fig. 2, and cells were harvested at the same time point. These cells were cultured in the presence of V3 peptide, and 48h later cell-free supernatants were collected and subjected to ELISA using the appropriate cytokine assay kits. The duplicate assays were performed and results are expressed as the means±s.e.m. of four to six mice. *, **, Significant difference between the Ubenimex (UBX)-formulated and unformulated groups (P <0.05 and P <0.01, respectively).
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