Engineering of immune responses to DNA immunization via co-delivery of costimulatory molecule genes.

Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.

Engineering of immune responses to DNA immunization via co-delivery of costimulatory molecule genes.

Conf Adv AIDS Vaccine Dev. 1997 May 4-7;:49. Unique Identifier : AIDSLINE MED/97927033
Kim JJ; Bagarazzi ML; Hu YD; Trivedi N; Chattergoon MA; Dang K; Agadjanyan MA; Mahalingam S; Boyer JD; Wang B; Weiner DB; University of Pennsylvania, Philadelphia, PA. Fax: (215) 573-9436.

Abstract: Costimulatory molecules play an important role in the induction of T cell-mediated immune responses. Effective T cell activation by APC requires two stimuli: the first signal originates from the binding of antigen-MHC and T cell receptor molecules which confers specificity. The second signal comes from the costimulatory proteins on APCs. The most potent costimulatory proteins are CD80 and CD86 costimulatory molecules. We investigated the role of the CD80 and CD86 molecules in the amplification of in vivo immune responses. We developed expression cassettes for CD80 and CD86 and analyzed their ability to function as in vivo modulators of the immune response induced by DNA immunization cassettes against HIV-1 antigen, pCEnv and pCGag/pol, by co-immunizing them into mice. We analyzed the immunological effects of co-immunization of these costimulatory molecule genes with DNA vaccines by looking at the magnitude of antigen-specific humoral and cellular immune responses. Although we did not see any significant change in the antigen-specific humoral response, we observed a dramatic increase in cytotoxic T lymphocyte induction as well as T helper cell proliferation with the co-administration of genes for CD86. This enhancement of CTLs was both MHC class I-restricted and CD8+ T cell-dependent. In contrast, co-immunization with CD80 expression cassette did not significantly increase T helper cell or CTL responses. These results demonstrate that CD86, and not CD80, can be engineered to direct the induction of antigen-specific T helper cell and cytotoxic T lymphocyte responses using DNA vaccines. Our findings demonstrate the power of this approach for optimizing DNA immunization by controlling the magnitude and direction of DNA vaccine-induced in vivo immune responses.

Keywords: *Antigens, CD/GENETICS *Antigens, CD80/GENETICS *Membrane Glycoproteins/GENETICS *Vaccines, DNA/IMMUNOLOGY
971130
M97B1189

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