DESIGN OF IMMUNOGENS AS COMPONENTS OF A NEW-GENERATION OF MOLECULAR VACCINES

Three new approaches to design effective immunogens are considered. At first, we derived an expression vector from bacteriophage M13 allowin g the exposure of short peptides on the virion surface. EIA demonstrat es that antibodies against a recombinant phage carrying the antigenic determinant of the HIV-1 gag protein reacted with the 17-kDa core prot ein of the virus and also with its polyprotein precursor p55 in immuno blotting. In another approach, we chose the hepatitis B core antigen ( HBcAg) particle as a vehicle for the presentation of foreign antigenic determinants to the immune system. Chimerical particles of HBcAg cont aining epitope of the VEE virus were obtained. A vector system for ins ertion of foreign antigenic determinants and production of both hybrid and wild HBcAg proteins were also obtained. The third approach relies on construction of immunogens from different T- and B-cell epitopes o f the HIV-1. We suggested to construct HIV-1 vaccines in a form of the TBI (T- and B-cell epitopes containing Immunogen) with a predetermine d tertiary structure, namely, a four-alpha-helix bundle. The gene of t he TBI protein consisting of nine HIV-1 epitopes was synthesized and e xpressed in Escherichia coli cells. Mice immunized with TBI showed hum oral and cellular immune responses to HIV-1. Anti-TBI antibodies displ ayed HIV-1 neutralizing activity. These new approaches offer promise i n the development of new effective vaccines.