Most synthetic peptide vaccines described to date are effective only in combination with proteins and Freund's adjuvant. The work describes a novel completely synthetic virus peptide vaccine, which consists of a synthetic activator of B cells and macrophages, covalently linked to an amphiphilic α-helical T-cell epitope. The low-molecular-weight vaccine of 3.4 kDa developed against foot-and-mouth disease virus (FMDV) is composed of a synthetic VP1 (135–154) with a sequence homologous to an FMDV protein and the adjuvant tripalmitoyl-S-glyceryl-cysteinylserylserine (P₃CSS). P₃CSS is the synthetic analogue of the N-terminal part of the lipoprotein from Gram-negative bacteria. The antigenic determinant VP1 (135–154) is an α-helix as shown by circular dichroism. The resulting novel type of vaccine tripalmitoyl-S-glyceryl-cysteinylserylseryl-FMDV-VP1 (135–154) induces a long-lasting high protection against foot-and-mouth disease and serotype-specific virus-neutralizing antibodies in guinea-pigs after a single administration without any additional adjuvant or carrier. In contrast to other simple fatty acid conjugates this new type of vaccine contains a built-in adjuvant with high affinity to both B and T lymphocytes.