A comparative study of different presentation strategies for an HIV peptide immunogen.
Different strategies have been used to increase the immunogenicity of an antigenic HIV peptide as a vaccine candidate. The selected B-cell epitope comprises 15 amino acids (317-331) of the V3 region of HIV-1, JY1 isolate (subtype D), in tandem with a T-helper epitope corresponding to the 830-844 region of tetanus toxoid. Several presentations, including oligomerization, multiple antigenic peptide dendrimers, and conjugation to dextran beads or to other macromolecular carriers, have been synthesized and evaluated. Murine sera from the different presentations of the V3 epitope have been compared with regard to antibody titers and cross-reactivity with heterologous HIV subtypes. The dendrimer version of the peptide conjugated to HBsAg protein was a better immunogen than the dendrimer alone and showed a higher immunogenicity than other multimeric presentations or than the peptide alone conjugated to dextran. The dendrimer version, either alone or conjugated to HBSAg, enhanced cross-reactivity toward heterologous V3 sequences relative to monomeric peptide. In addition, fine epitope mapping of the entire JY1 sequence by sera from the different immunization groups was performed by the spot synthesis technique. Results showed that the amino acids involved in molecular recognition were LXQXXY or LXQXLY, with particularly strong recognition of the C-terminal region LGQALY. However, cross-reactivity toward the heterologous sequences did not completely correlate with recognition of particular amino acids in the primary sequences. These results can find application in the development of HIV vaccine candidates.
Cruz
Luis J
LJ
Barcelona Institute of Biomedical Research, Barcelona Science Park, 08028 Barcelona, Spain.
Iglesias
Enrique
E
Aguilar
Julio C
JC
González
Luis J
LJ
Reyes
Osvaldo
O
Albericio
Fernando
F
Andreu
David
D
D016915:AIDS Vaccines / Q000138:chemical synthesis* / Q000276:immunology; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology; D005260:Female; D015497:HIV-1 / Q000276:immunology; D007115:Immunization Schedule; D007202:Indicators and Reagents; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013601:T-Lymphocytes / Q000276:immunology; D022223:Vaccines, Subunit / Q000138:chemical synthesis* / Q000276:immunology; D014614:Vaccines, Synthetic / Q000737:chemistry* / Q000276:immunology
D016915:AIDS Vaccines; D000596:Amino Acids; D000939:Epitopes; D007202:Indicators and Reagents; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic