Orientation of epitopes influences the immunogenicity of synthetic peptide dimers.

The immunogenicity of synthetic peptide dimers based on epitope sequences derived from the mycobacterial 65-kDa antigen and the foot and mouth disease virus (FMDV) VP1 protein was examined in inbred mice. The analysis was directed towards the potential helper role of a T cell stimulatory mycobacterial epitope (65-85) with respect to poorly immunogenic sites either from the same molecule (422-436) or from VP1 (141-160). The 65-85 repeat homodimer induced an antibody response in CBA/ca but not in C57BL/6 mice, both nonresponders to the 65-85 monomer, and amplified the antibody response in BALB/c, monomer-responder mice.

A high proportion of anti-peptide antibodies recognize foot-and-mouth disease virus particles.

Synthetic peptides representing the amino acid sequence 141-160 of the structural protein VP1 of foot-and-mouth disease virus (FMDV) elicit virus-neutralizing antibody. Absorption of anti-peptide sera with purified virus particles removed all detectable virus-binding and neutralizing activity, and reduced the ELISA titres against the homologous peptide by 31-41%. The proportion of anti-peptide antibodies that also recognized virus was unaffected by whether the peptide had been inoculated free, carrier-linked or as part of a fusion protein.

Non-responsiveness to a foot-and-mouth disease virus peptide overcome by addition of foreign helper T-cell determinants.

Study of the immune response to synthetic antigens has shown that uncoupled peptides can realize their potential as vaccines only if they contain domains that react with helper T-cell receptors and Ia antigens in addition to antibody binding sites. Here we consider whether genetically restricted non-responsiveness to an uncoupled peptide could be overcome by synthesizing a peptide with an additional helper T-cell epitope from a different protein. We demonstrate that H-2d mice, which are non-responders to the 141-160 VP1 peptide of foot-and-mouth disease virus (FMDV), can be converted into responders by immunization with peptides containing the FMDV sequence with defined 'foreign' helper T-cell determinants from ovalbumin or sperm whale myoglobin.

Improved immunogenicity of a peptide epitope after fusion to hepatitis B core protein.

Synthetic vaccines for viral diseases can use defined regions of viral proteins as immunogens: the peptide sequence of amino acids 141-160 of the VP1 protein of foot and mouth disease virus (FMDV) elicits virus-neutralizing antibodies to protect guinea pigs, cattle and pigs either when coupled to a carrier protein or when administered in liposomes or in incomplete Freund's adjuvant. The immune response to these peptides is much lower than that to complete virus particles and the same sequence fused to the N terminus of beta-galactosidase did not produce a more potent immunogen than synthetic peptide alone. We report here an expression system for immunogenic epitopes linked to a carrier protein, hepatitis B core antigen, to form part of a virus-like complex which can present these epitopes to the immune system at high density.

A synthetic peptide which elicits neutralizing antibody against human rhinovirus type 2.

Synthetic peptides corresponding to six predicted immunogenic sites on human rhinovirus type 2 (HRV2) have been tested for their reactivity with an anti-virion antibody and for their ability to elicit neutralizing antibody. Four of the peptides reacted with HRV2 antiserum in an indirect ELISA. Rabbit antisera produced to three of these four peptides, one each from VP1, VP2 and VP3, reacted with the virus in an indirect ELISA and with the corresponding proteins by Western blotting.