title: Tat-neutralizing antibodies in vaccinated macaques.
abstract: The human immunodeficiency virus Tat protein is essential for virus replication and is a candidate vaccine antigen. Macaques immunized with Tat or chemically modified Tat toxoid having the same clade B sequence developed strong antibody responses. We compared these antisera for their abilities to recognize diverse Tat sequences. An overlapping peptide array covering three clade B and two clade C Tat sequences was constructed to help identify reactive linear epitopes. Sera from Tat-immunized macaques were broadly cross-reactive with clade B and clade C sequences but recognized a clade B-specific epitope in the basic domain. Sera from Tat toxoid-immunized macaques had a more restricted pattern of recognition, reacting mainly with clade B and with only one clade B basic domain sequence, which included the rare amino acids RPPQ at positions 57 to 60. Monoclonal antibodies against the amino terminus or the domain RPPQ sequence blocked Tat uptake into T cells and neutralized Tat in a cell-based transactivation assay. Macaques immunized with Tat or Tat toxoid proteins varied in their responses to minor epitopes, but all developed a strong response to the amino terminus, and antisera were capable of neutralizing Tat in a transactivation assay.
authors.affiliation: Institute of Human Virology, University of Maryland Biotechnology Institute, Baltimore, Maryland 21201, USA.
authors.forename: Ilia
authors.initials: I
authors.lastname: Tikhonov
authors.forename: Tracy J
authors.initials: TJ
authors.lastname: Ruckwardt
authors.forename: Glen S
authors.initials: GS
authors.lastname: Hatfield
authors.forename: C David
authors.initials: CD
authors.lastname: Pauza
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D015696:Gene Products, tat / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D015483:HIV Antibodies / Q000097:blood* / Q000276:immunology*; D015658:HIV Infections / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology; D006367:HeLa Cells; D006801:Humans; D007114:Immunization; D019169:Jurkat Cells; D008251:Macaca; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D015533:Transcriptional Activation; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D015696:Gene Products, tat; D015483:HIV Antibodies; D010455:Peptides; D054322:tat Gene Products, Human Immunodeficiency Virus