Use of Fusion Proteins and Procaryotic Display Systems for Delivery of HIV-1 Antigens: Development of Novel Vaccines for HIV-1 Infection

Piergiuseppe   De   Berardinis; Rossella      Sartorius; Antonella      Caivano; Dina      Mascolo; Gonzalo   J.   Domingo; Giovanna   Del   Pozzo; Muriel      Gaubin; Richard   N.   Perham; Dominique      Piatier-Tonneau; John      Guardiola

Abstract

Two non-pathogenic scaffolds (represented by the filamentous bacteriophage fd and the dihydrolipoyl acetyltransferase E2 protein of the Bacillus stearothermophilus pyruvate dehydrogenase (PDH) complex) able to deliver human immunodeficiency virus (HIV)-1 antigenic determinants, were designed in our laboratories and investigated in controlled assay conditions. Based on a modification of the phage display technology, we developed an innovative concept for a safe and inexpensive vaccine in which conserved antigenic determinants of HIV-1 reverse transcriptase (RTase) were inserted into the N-terminal region of the major pVIII coat protein of bacteriophage fd virions. Analogously, we developed another antigen delivery system based on the E2 component from the PDH complex and capable of displaying large intact proteins on the surface of an icosahedral lattice. Our data show that both of these systems can deliver B and T epitopes to their respective presentation compartments in target cells and trigger a humoral response as well as a potent helper and cytolytic response in vitro and in vivo.

Keywords: vaccine, filamentous bacteriophage fd, phage display, dihydrolipoyl acetyltransferase

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