DESIGN OF A 4-HELIX-BUNDLE PROTEIN AS A POTENTIAL VACCINE AGAINST HUMAN-IMMUNODEFICIENCY-VIRUS (HIV-1)

Efficient synthetic new-generation vaccines must contain various T- an d B-cell epitopes of the infectious agent. It is proposed to construct the vaccines as proteins of preset tertiary structure. A possibility of using in the vaccine design the well-known spatial motif-four-alpha -helix bundle-is substantiated. Antigenic determinants of cellular (am phipathic alpha-helices) and humoral immunity (flexible hydrophilic lo ops) are used as blocks for constructing the vaccine. Nonloop B epitop es and nonhelical T epitopes can be introduced into the protein N- and C-terminal regions. The experimentally studied T- and B-cell epitopes of HIV-1 were analyzed; four T-cell and five B-cell epitopes from gen es env and gag were chosen to compose the vaccine protein. The predict ed secondary structure and the antigenic determinants of the polypepti de thus constructed conformed to the design sought for. The amino acid composition of the protein corresponded to that of water-soluble glob ular proteins. A gene coding for this protein was synthesized. The adv antages and limitations of the proposed approach to vaccine constructi on are discussed.