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Important B-cell epitopes for neutralization of human immunodeficiency virus type 1 Tat in serum samples of humans and different animal species immunized with Tat protein or peptides

C. Desgranges^1,

¹ E03-34 INSERM, Institut de Génétique Moléculaire, Hôpital St Louis, 27 rue Juliette Dodu, 75010 Paris, France
² UPR9021 CNRS, Institut de Biologie Moléculaire et Cellulaire, 67000 Strasbourg, France
³ Centre de Recherches des Cordeliers, Université Pierre et Marie Curie, 75005 Paris, France

Correspondence
C. Desgranges
claude.desgranges{at}chu-stlouis.fr

The Tat regulatory protein of human immunodeficiency virus type 1 (HIV-1) is secreted by infected cells and plays a key role in viral pathogenesis and replication. Tat protein has been proposed as a target antigen for vaccine design since anti-Tat antibodies may interfere with virus spread and disease progression. The aim of this study was to analyse the serum antibody response of mice, rabbits, macaques and humans immunized with recombinant Tat, synthetic Tat, Tat toxoid or Tat peptides and to examine the biological properties of these antibodies in terms of Tat-induced transactivation and HIV-1 replication. Only sera with antibody specificity to both N-terminal and basic functional domains were able to inhibit extracellular Tat-dependent transactivation significantly in vitro. Antibodies from a human subject immunized with Tat also reduced HIV-1 replication in acutely infected T cells and blocked reactivation of virus replicating low levels in chronically infected cells by exogenous Tat. These results demonstrate that immunization with Tat protein or a combination of synthetic Tat peptides elicits the production of Tat-neutralizing serum antibodies and suggest that Tat vaccination could be used to block in vivo extracellular Tat autocrine/paracrine transactivation of HIV-1 replication.

Present address: UPR 2228 CNRS, 45 rue des Saint-Pères, 75006 Paris, France.