Molecular dynamics of the alpha-helical epitope of a novel synthetic lipopeptide foot-and-mouth disease virus vaccine.
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 alpha-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 alpha-helix, as shown by CD. Molecular dynamics simulations (MDS) carried out using the highly homologous alpha-helical alcohol dehydrogenase (ADH) segment H3 as starting conformation for VP1(138-149) suggest that the FMDV segment 138-149 may adopt alpha-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.
Krug
M
M
Folkers
G
G
Haas
B
B
Hess
G
G
Wiesmüller
K H
KH
Freund
S
S
Jung
G
G
D000595:Amino Acid Sequence; D005537:Aphthovirus / Q000276:immunology*; D000939:Epitopes; D008074:Lipoproteins / Q000276:immunology; D008969:Molecular Sequence Data; D011487:Protein Conformation; D014612:Vaccines; D014614:Vaccines, Synthetic; D014765:Viral Vaccines
D000939:Epitopes; D008074:Lipoproteins; D014612:Vaccines; D014614:Vaccines, Synthetic; D014765:Viral Vaccines