Xenogeneic and allogeneic anti-MHC immune responses induced by plasmid DNAimmunization

Major histocompatibility complex (MHC) proteins are known to be incorporate d into the human immunodeficiency virus (HIV-1) envelope as the virion buds from the host cell surface. Studies using simian immunodeficiency virus (S IV) infection of macaques have demonstrated that immunization with uninfect ed human cells or purified HLA proteins can provide protection from challen ge with live SIV when it is grown in human cells expressing the same MHC al leles. Thus the induction of anti-MHC immune responses represents an import ant option to consider with respect to vaccine design for SIV and HIV. Here we examine plasmid DNA immunization strategies as an alternative to cellul ar or protein immunogens for the induction of xenogeneic and allogeneic imm une responses in C57BL/6 mice and in an HLA transgenic mouse model system, respectively. We compared the immunogenicity of HLA-A2- and HLA-B27-express ing;pressing splenocytes with the corresponding plasmid DNA immunogens. Res ults from the transgenic mouse experiments indicate that plasmid DNA immuni zation with both class I and class II MHC-encoding vectors can elicit antib ody responses recognizing conformationally intact MHC molecules. Our data a lso show that immunization with class I MHC-encoding DNA immunogens can eli cit cytotoxic T-lymphocyte responses, demonstrating the potential to mobili ze both antibody and cell-mediated anti-MHC immune responses in the context of this approach to HIV-I vaccine design. (C) 1999 Elsevier Science Ltd. A ll rights reserved.