Synthetic peptides as the basis for vaccines against influenza virus and bacterial toxins

Abstract

Synthetic peptides which comprise relevant epitope(s) of disease-causing agents were used as a basis for vaccine development. An alternative approach is based on recombinant DNA technology, employing synthetic oligonucleotides which code for relevant peptide epitopes. The peptides corresponding to the regions 8–20 and 50–64 of the B subunit of Cholera toxin, when conjugated to tetanus toxin, induced neutralizing antibodies against the native toxin as well as against the homologous heat labile toxin of toxigenic E. coli. In the case of Shiga toxin, several peptides from the amino- and carboxytermini of the B-chain, in macromolecular conjugates or polymers, led to efficient systemic and local immunity, manifested in both neutralizing antibodies and in vivo protection of the mice and rats against the detrimental effects of the toxin. Expression of these peptides as recombinant products led to similar protective effects. A peptide corresponding to the sequence 91–108 of influenza haemagglutinin, conjugated to tetanus toxoid, elicited antibodies which reacted with several strains of H3 influenza virus and neutralized their biological functions. Mice immunized with this conjugate were partially protected against infection. Furthermore, coupling of muramyldipeptide (MDP) to this conjugate led to a synthetic vaccine with built-in adjuvanticity. A synthetic recombinant vaccine, in which this epitope was expressed in Salmonella flagellin, induced partial protection by intranasal immunization without the aid of adjuvant.