Identification of immunodominant epitopes in inactivated Tat-vaccinated healthy and HIV-1-infected volunteers.
We analyzed the epitopes and the molecular forms of Tat recognized by the antibodies raised by Tat-toxoid vaccination in both healthy and HIV-infected volunteers. Tat-toxoid-vaccinated healthy volunteer sera reacted predominantly with peptides covering amino acids 1 through 24 and 46 through 60, corresponding to the N-terminus and basic domains of Tat. In contrast, whereas all sera from vaccinated HIV-1-positive patients reacted with the N-terminus and (with a single exception) with the basic domain, most of these sera also recognized peptides encompassing distinct domains of Tat, particularly the C-terminus (79-86). The sera of vaccinated individuals recognized both monomeric and oligomeric forms of Tat 1 through 86 or of Tat 1 through 101 and also blocked the ability of cell-released extracellular Tat to transactivate the HIV-1 LTR promoter. Synthetic Tat preincubated with sera from vaccinated individuals lost its functional activity as well. This is probably because of its inability to enter the cells as a result of immune complex formation with anti-Tat IgG. These data demonstrate that Tat-toxoid vaccination induces an efficient antibody response blocking the functional activity of Tat.
Noonan
Douglas M
DM
Tumor Progression Section, double dagger Immuno-Pharmacology Section, and #Molecular Biology Laboratory, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Gringeri
Alessandro
A
Meazza
Raffaella
R
Rosso
Ombretta
O
Mazza
Stefania
S
Muça-Perja
Myrvet
M
Le Buanec
Hélène
H
Accolla
Roberto S
RS
Albini
Adriana
A
Ferrini
Silvano
S
D016915:AIDS Vaccines / Q000276:immunology*; D000328:Adult; D000595:Amino Acid Sequence; D005260:Female; D015696:Gene Products, tat / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology / Q000494:pharmacology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007106:Immune Sera / Q000276:immunology / Q000494:pharmacology; D016056:Immunodominant Epitopes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects; D015164:Vaccines, Inactivated / Q000276:immunology*; D014838:Volunteers; D054322:tat Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D015696:Gene Products, tat; D015483:HIV Antibodies; D007106:Immune Sera; D016056:Immunodominant Epitopes; D015164:Vaccines, Inactivated; C421254:human immunodeficiency virus type 1 Tat vaccine; D054322:tat Gene Products, Human Immunodeficiency Virus