Induction of neutralizing antibodies against human immunodeficiency virus type 1 using synthetic peptide constructs containing an immunodominant T-helper cell determinant from vpr.
Identification of immunodominant T-helper-cell determinants after natural infection is an important step in the design of immunogens for potential use in vaccination. Using cells from human immunodeficiency virus type 1 (HIV-1)-infected individuals and a panel of peptides encompassing the sequence of the regulatory protein vpr from HIV-1, we identified the T-helper determinant QLLFIHFRIGCRHSR, which is active in 37.5% of these individuals. To gain insight on the efficacy of this peptide in helping induce neutralizing antibodies against a B-cell determinant (BD), we synthesized constructs containing B- and T-cell determinants and tested them in BALB/c mice, the highest responders to the T-cell determinant moiety among several strains tested. These immunogens induced antibodies against two chosen B-cell determinants from HIV-1IIIB gp160 (amino acids 310-322 from the V3 loop of gp120 and 736-751 from gp41) that were able to neutralize HIV-1 infection in vitro. The highest neutralization titer against HIV-1IIIB was obtained by immunization with the homopolymer of the construct containing the T-cell epitope from vpr and the B-cell epitope from the V3 loop. We believe that the immunodominant T-cell determinant from vpr is a promising epitope to consider in the design of future peptide vaccines.
Sarobe
P
P
Departamento de Medicina Interna, Universidad de Navarra, Pamplona, Spain.
Lasarte
J J
JJ
Golvano
J J
JJ
Prieto
I
I
Gullón
A
A
Soto
M J
MJ
Labarga
P
P
Prieto
J
J
Borrás-Cuesta
F
F
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D015686:Gene Products, env / Q000276:immunology; D016336:Gene Products, vpr / Q000737:chemistry / Q000276:immunology*; D015483:HIV Antibodies / Q000096:biosynthesis*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007114:Immunization; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D011498:Protein Precursors / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D054325:vpr Gene Products, Human Immunodeficiency Virus
D015686:Gene Products, env; D016336:Gene Products, vpr; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; C059762:HIV envelope protein gp120 (305-321); D007106:Immune Sera; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D011498:Protein Precursors; D054325:vpr Gene Products, Human Immunodeficiency Virus