[Design of four-helix protein--a possible vaccine against human immunodeficiency virus (HIV-1)]

Successful approach to the development of safe and effective synthetic vaccines requires that different B- and T-cell epitopes of the infectious agent be included into the vaccine construction. It is suggested that vaccines should be constructed as proteins with both optimal epitope composition and predetermined tertiary structure. Based on analysis of B-cell and T-cell epitope properties, a possibility to use one well-known protein spatial motif--four-alpha-helix bundle--for vaccine construction is substantiated. Antigenic determinants of cellular immunity (amphipathic alpha-helices) and humoral immunity (flexible hydrophilic loop regions) can be used as blocks for vaccine design. Nonloop B-epitopes and nonhelical T-epitopes may be introduced in the protein N- and C-terminal regions. General principles of PTS-vaccine construction have been applied to anti-HIV-1 vaccine design. Experimentally studied T- and neutralizing B-cell epitopes from HIV-1 proteins were analyzed. The sequence of one possible four-alpha-helix protein vaccine has been constructed. Predicted secondary structure and T- and B-cell epitopes of this protein coincided with the planned ones. The amino acid composition of the protein was found to be consistent with the composition of globular water-soluble proteins. The gene of the protein with codon composition optimal for expression in E. coli has been synthesized. The advantages and limitations of this approach to vaccine design are discussed.