Modifying the HIV-1 env gp160 gene to improve pDNA vaccine-elicited cell-mediated immune responses.

Plasmid DNA (pDNA) vaccines are effective at eliciting immune responses in a wide variety of animal model systems, however, pDNA vaccines have generally been incapable of inducing robust immune responses in clinical trials. Therefore, to identify means to improve pDNA vaccine performance, we compared various post-transcriptional and post-translational genetic modifications for their ability to improve antigen-specific CMI responses. Mice vaccinated using a sub-optimal 100 mcg dose of a pDNA encoding an unmodified primary isolate HIV-1(6101) env gp160 failed to demonstrate measurable env-specific CMI responses.

A dose sparing effect by plasmid encoded IL-12 adjuvant on a SIVgag-plasmid DNA vaccine in rhesus macaques.

An experimental pDNA vaccine adjuvant expressing IL-12 was evaluated for its ability to augment the humoral and cellular immune responses elicited by a SIVmac239 gag p39 expressing pDNA vaccine. To determine the effect of vaccine dose on the immune response, rhesus macaques were immunized with 1.5 mg or 5.

Comparison of antibody titers after immunization with monovalent or tetravalent KLH conjugate vaccines.

Antigens such as ganglioside GD3, neutral glycolipid Lewis(y) (Le(y)) and mucins MUC1 and MUC2 are over-expressed on the cell surface of many tumors. We have shown previously that conjugation of antigens such as these to keyhole limpet hemocyanin (KLH) and the use of immunological adjuvant QS-21 is the optimal approach for inducing high titer IgM and IgG antibodies. These antibodies are able to bind with natural antigens on the tumor cell surface and mediate complement dependent cytotoxicity and/or antibody dependent cell mediated cytotoxicity.