IMMUNOGENICITY EVALUATION OF A LIPIDIC AMINO ACID-BASED SYNTHETIC PEPTIDE VACCINE FOR CHLAMYDIA-TRACHOMATIS

Lipidic amino acid-based synthetic peptides derived from the variable domains (VD) of Chlamydia trachomatis outer membrane protein 1 were ev aluated as potential candidate sequences in a vaccine. A peptide seque nce designated P2 from the VD IV of serovar B contained a B cell epito pe capable of eliciting antibodies binding to serovar B elementary bod ies (EB) and a T helper site capable of presentation by multiple H-2 a lleles. Polymerization of the P2 into polylysine to form lipid core pe ptides (LCP) significantly enhanced immunogenicity compared with P2 mo nomer alone. The LCP system incorporates lipidic amino acids into the polylysine system and enhances lipophobicity and membrane binding effe cts of the peptide. A second peptide sequence derived from the VD I of serovar C was cosynthesized with P2 into lipidic polylysine LCP and w as designated LCP-H1. Antibodies to this construct reacted at high tit er with EB of the three major trachoma causing C trachomatis serovars A, B, and C. LCP-H1 was immunogenic among four of five murine H-2 alle les. Pepscan analysis showed that the fine specificity of antibodies g enerated to LCP-H1 were directed to the predetermined neutralizing epi tope sequences. An in vitro HAK cell neutralization assay showed that LCP-H1 elicited neutralizing antibodies to serovars A, B, and C, but t hese were of low titer. Because LCP-H1 antibodies bound to the peptide sequence with 10-100-fold higher titer than to EB, the low neutraliza tion titers most likely result from conformational differences between the synthetic peptide and antigenic sites on the native organism. Mod ification of LCP-H1 to incorporate a predefined conformation may resul t in improved antigenic properties.