Design of immunogens as components of a new generation of molecular vaccines

• Published in: Journal of biotechnology Vol. 44; no. 1; pp. 129 - 137
• Main Authors: Loktev, V.B., Ilyichev, A.A., Eroshkin, A.M., Karpenko, L.I., Pokrovsky, A.G., Pereboev, A.V., Svyatchenko, V.A., Ignat'ev, G.M., Smolina, M.I., Melamed, N.V., Lebedeva, C.D., Sandakhchiev, L.S.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 26.01.1996
• Subjects: AIDS Vaccines; AIDS/HIV; Amino Acid Sequence; Animals; Antigens, Viral - chemistry; Antigens, Viral - genetics; Antigens, Viral - immunology; Artificial protein; Bacteriophage M13; Base Sequence; Biotechnology; DNA Primers; Drug Design; Encephalitis Virus, Eastern Equine - genetics; Encephalitis Virus, Eastern Equine - immunology; Encephalitis Virus, Venezuelan Equine - genetics; Epitope; Epitopes - chemistry; Epitopes - immunology; Escherichia coli; Gene Products, gag - genetics; Gene Products, gag - immunology; Genes, gag; Hepatitis B Core Antigens - biosynthesis; Hepatitis B Core Antigens - immunology; HIV-1; HIV-1 - immunology; Horses; Humans; Immunogenicity; Mice; Models, Structural; Molecular Sequence Data; Phage; Protein Structure, Secondary; Sequence Homology, Amino Acid; T-Lymphocytes - immunology; Vaccine; Vaccines, Synthetic; VEE; Viral Vaccines; Virus; HIV-1; Virus; Artificial protein; Epitope; Immunogenicity; VEE; Vaccine; Phage
• ISSN: 0168-1656; 1873-4863
• DOI: 10.1016/0168-1656(95)00089-5

Three new approaches to design effective immunogens are considered. At first, we derived an expression vector from bacteriophage M13 allowing the exposure of short peptides on the virion surface. EIA demonstrates that antibodies against a recombinant phage carrying the antigenic determinant of the HIV-1 gag protein reacted with the 17-kDa core protein of the virus and also with its polyprotein precursor p55 in immunoblotting. 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 containing epitope of the VEE virus were obtained. A vector system for insertion 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 of 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 predetermined tertiary structure, namely, a four-α-helix bundle. The gene of the TBI protein consisting of nine HIV-1 epitopes was synthesized and expressed in Escherichia coli cells. Mice immunized with TBI showed humoral and cellular immune responses to HIV-1. Anti-TBI antibodies displayed HIV-1 neutralizing activity. These new approaches offer promise in the development of new effective vaccines.