Mimotopes selected with antibodies from HIV-1-neutralizing long-term non-progressor plasma.
A promising approach to identify HIV-1 vaccine candidates is to dissect the natural immune response against the virus in persons controlling the infection over decades without any antiviral therapy. Here we focus on a group of such persons, eight long-term non-progressors (LTNP), in which we proved the presence of broadly neutralizing antibodies against HIV-1 in the plasma as very likely cause for their LTNP status. The aim of this study was to identify the epitopes for these neutralizing antibodies, as these should represent immunogens potentially able to elicit neutralizing antibodies upon vaccination. We screened random peptide phage libraries with plasma antibodies from eight LTNP. After several rounds of positive and negative selection, about 700 HIV-specific mimotopes were sequenced. The mimotope sequences were analyzed for homology to HIV-1 Env, in particular for their capacity to represent conformational epitopes on the surface of the gp120 structure using our software 3DEX. Related phage groups were analyzed for crossreactivity with the LTNP plasma by ELISA as well as for their capacity to induce HIV-1-neutralizing antibodies in mice. Based on this study interesting mimotopes can now be selected for further immunization studies.
Humbert
Michael
M
Georg-Speyer-Haus, Institute for Biomedical Research, Frankfurt am Main, Germany.
Antoni
Sascha
S
Brill
Boris
B
Landersz
Margot
M
Rodes
Berta
B
Soriano
Vicente
V
Wintergerst
Uwe
U
Knechten
Heribert
H
Staszewski
Schlomo
S
von Laer
Dorothee
D
Dittmar
Matthias T
MT
Dietrich
Ursula
U
D000595:Amino Acid Sequence; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D015483:HIV Antibodies / Q000097:blood* / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D051379:Mice; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D019151:Peptide Library; D017386:Sequence Homology, Amino Acid
D018985:Epitopes, B-Lymphocyte; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D019151:Peptide Library