Structural and immunogenicity analysis of chimeric B-cell epitope constructs derived from the gp46 and gp21 subunits of the envelope glycoproteins of HTLV-1.
B-cell epitopes were selected from the gp21 and gp46 subunits of the envelope glycoprotein of human T-cell lymphotropic virus type 1 (HTLV-1) by computer-aided analyses of protein antigenicity. Molecular modeling was used to design and synthesize the epitopes as chimeric constructs with promiscuous T-helper epitopes derived either from the tetanus toxoid (amino acids 947-967) or measles virus fusion protein (amino acids 288-302). Circular dichroism measurements revealed that the peptides had a secondary structure that correlated well with the crystal structure data or predicted structure. The chimeric peptides were then evaluated for their immunogenicity in rabbits or mice. Antibodies against one of the epitopes derived from the gp21 subunit were found to be neutralizing in its ability to inhibit the formation of virus-induced syncytia. These studies underscore the importance of the gp21 transmembrane region for the development of vaccine candidates. The applicability of a chimeric approach is discussed in the context of recent findings regarding the role of gp21 transmembrane region in the viral fusion process.
Department of Obstetrics and Gynecology, The Ohio State University, Columbus, OH 43210, USA.
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Sundaram
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Beebe
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Kaumaya
D000818:Animals; D045744:Cell Line, Tumor; D002942:Circular Dichroism; D017076:Computer-Aided Design; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry* / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology; D015686:Gene Products, env / Q000138:chemical synthesis / Q000276:immunology*; D015726:Giant Cells / Q000187:drug effects; D015481:HTLV-I Antibodies / Q000302:isolation & purification / Q000494:pharmacology; D015486:HTLV-I Antigens / Q000737:chemistry* / Q000276:immunology*; D007114:Immunization; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D011817:Rabbits; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000276:immunology; D015682:Retroviridae Proteins, Oncogenic / Q000138:chemical synthesis / Q000276:immunology*; D013745:Tetanus Toxoid / Q000138:chemical synthesis / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus
D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D015686:Gene Products, env; D015481:HTLV-I Antibodies; D015486:HTLV-I Antigens; D010455:Peptides; D011993:Recombinant Fusion Proteins; D015682:Retroviridae Proteins, Oncogenic; D013745:Tetanus Toxoid; D054299:env Gene Products, Human Immunodeficiency Virus; C055265:gp21 protein, Human T-lymphotropic virus 1; C055266:gp46 protein, Human T-cell leukemia virus type I