Molecular dynamics of the α-helical epitope of a novel synthetic lipopeptide foot-and-mouth disease virus vaccine

Publisher Website
Google Scholar
Abstract
A novel synthetic foot‐and‐mouth disease virus (FMDV) peptide vaccine consisting of a synthetic B‐cell and macrophage activator covalently linked to an amphiphilic α‐helical T‐cell epitope was developed. The low molecular weight vaccine of 3400 daltons is composed of virus VP1 antigenic determinant and the immunologically active lipotripeptide tripalmitoyl‐S‐glyceryl‐cysteinyl‐seryl‐serine (P3CSS) as built‐in adjuvant. The vaccine, tripalmitoyl‐S‐glyceryl‐cysteinyl‐seryl‐seryl‐FMDV‐VP1 (VP1 = serotype O1K 135–154) induces protection against homologous challenge and serotype‐specific virus neutralizing antibodies in guinea pigs after single administration without further adjuvants or carriers. A P3CSS conjugate with the FMDV‐VP1 segment 135–154 of strain O Wuppertal produced only poor cross‐protection against challenge with O1K virus. The antigenic determinant VP1(135–154) is an amphiphilic α‐helix, as shown by CD. Molecular dynamics simulations (MDS) carried out using the highly homologous α‐helical alcohol dehydrogenase (ADH) segment H3 as starting conformation for VP1(138–149) suggest that the FMDV segment 138–149 may adopt α‐helical conformation during binding to its T‐cell receptor, and that the development of the system during MDS may be considered as the dissociation step of the complex.