Peptide based vaccine design: synthesis and immunological characterization of branched polypeptide conjugates comprising the 276-284 immunodominant epitope of HSV-1 glycoprotein D.
The importance of the length and conjugation site of a protective epitope peptide (276SALLEDPVG284) from glycoprotein D of herpes simplex virus in branched polypeptide conjugates has been investigated. A new set of peptides, with a single attachment site and truncated sequences, was prepared. The immunogenicity of conjugates and the specificity of antibody responses elicited were investigated in BALB/c, C57/B1/6 and CBA mice. It was found that the covalent coupling of the peptide comprising the 276-284 sequence of gD through its Asp residue at position 281 did not influence the immunogenic properties of the epitope, while involvement of the side chain of Glu at position 280 almost completely abolished immunogenicity. These results clearly indicated that the conjugation site of the epitope peptide influenced the intensity and specificity of antibody responses. Comparison of the immunological properties of conjugates containing truncated gD peptides revealed the presence of two epitopes within the 276-284 region. One of the proposed epitopes is situated at the N-terminal (276-281) region, while the other is located at the C-terminal end of the sequence (279-284). Binding data demonstrated that some of the peptides comprising these epitopes induced gD-specific responses in their conjugated form and also elicited an immune response that conferred protection against lethal HSV-1 infection. The correlation of peptide- and gD-specific antibody responses with the protective effect of the immune response is discussed.
Mezo
Gábor
G
Research Group of Peptide Chemistry, Hungarian Academy of Sciences, Eötvös L. University, Budapest.
Dalmadi
Balazs
B
Mucsi
Ilona
I
Bosze
Szilvia
S
Rajnavölgyl
Eva
E
Hudecz
Ferenc
F
D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid; D000939:Epitopes / Q000737:chemistry*; D018259:Herpesvirus 1, Human / Q000378:metabolism*; D013058:Mass Spectrometry; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D013997:Time Factors; D022223:Vaccines, Subunit / Q000138:chemical synthesis* / Q000276:immunology; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000378:metabolism*
D000596:Amino Acids; D000939:Epitopes; D010455:Peptides; D022223:Vaccines, Subunit; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1