RECOGNITION OF PROMINENT VIRAL EPITOPES INDUCED BY IMMUNIZATION WITH HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REGULATORY GENES

Mice immunized with the regulatory genes nef, rev, and tat from human immunodeficiency virus type 1 developed both humoral and cellular immu ne responses to the gene products Nef, Rev, and Tat. This study demons trates that it is feasible to induce immune reactions to all of these regulatory gene products. Humoral responses were seen after DNA boosts , while potent T-cell proliferative responses were noted already after a single immunization. A Th1-directed immune response was demonstrate d early after immunization. A 3- to 75-fold-stronger T-cell response m as seen in animals receiving DNA epidermally compared to that in anima ls receiving intramuscular injections. Nef, Rev, and Tat putative B- a nd T-cell epitopes were clearly mapped by using peptides derived from the regulatory proteins and were similar to those which are detected i n human immunodeficiency virus infection. Although immunization by the Nef, Rev, and Tat proteins raised high immunoglobulin G titers in ser um, the epitope spreading appeared broader after DNA immunization, The combination of all of these regulatory genes together with two genes for structural proteins, the envelope and gag genes, demonstrated that a combined approach is feasible in that reactivities to all antigens persisted or were even augmented. No interference between plasmids was noted.