Epitope mapping of the 273-284 region of HSV glycoprotein D by synthetic branched polypeptide carrier conjugates.
To investigate the antigenicity of a predicted epitope region of herpes simplex virus gD, peptides comprising the 273-284 sequence have been synthesized and conjugated to a branched polypeptide with polylysine backbone (poly[L-Lys-(DL-Alam)], AK). In order to analyze the effect of the carrier on the solution conformation of the potential peptide-epitopes, three peptides (273-284, 273-281 and 276-284) and their polypeptide conjugates were studied by CD spectroscopy in PBS or in TFE. In immunized BALB/c and CBA mice, the level of peptide-, conjugate- and carrier-specific antibody responses were measured. Conjugates with synthetic polypeptide carrier AK induced epitope-specific IgG responses, accompanied by the appearance of a low level of carrier-specific antibodies. The cross-reactivity pattern of induced antibodies revealed the presence of at least two functionally distinct, overlapping epitopes, the availability of which was influenced by flanking residues at the N-terminus. Preimmunization of BALB/c or CBA mice with the [276-284]-AK conjugate resulted in the production of HSV-specific antibodies and in prolonged survival of animals infected with a lethal dose of herpes simplex virus. The degree of protection was comparable to that of [1-23]-AK conjugate (30).
Hudecz
F
F
Research Group of Peptide Chemistry, Hungarian Academy of Sciences; Eötvös L. University, Budapest.
Hilbert
A
A
Mezö
G
G
Mucsi
I
I
Kajtár
J
J
Bösze
S
S
Kurucz
I
I
Rajnavölgyi
E
E
D000409:Alanine / Q000031:analogs & derivatives; D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D002942:Circular Dichroism; D003429:Cross Reactions; D004337:Drug Carriers; D000939:Epitopes / Q000032:analysis*; D006561:Herpes Simplex / Q000517:prevention & control; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D011107:Polylysine / Q000031:analogs & derivatives; D018139:Simplexvirus / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000276:immunology*
D000914:Antibodies, Viral; D004337:Drug Carriers; D000939:Epitopes; D010446:Peptide Fragments; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1; C040570:glycoprotein D-herpes simplex virus type 2; C062592:poly(lysine(alanine)); D011107:Polylysine; D000409:Alanine