title: Design and characterization of a peptide mimotope of the HIV-1 gp120 bridging sheet.
abstract: The Bridging Sheet domain of HIV-1 gp120 is highly conserved among the HIV-1 strains and allows HIV-1 binding to host cells via the HIV-1 coreceptors. Further, the bridging sheet domain is a major target to neutralize HIV-1 infection. We rationally designed four linear peptide epitopes that mimic the three-dimensional structure of bridging sheet by using molecular modeling. Chemically synthesized peptides BS3 and BS4 showed a fair degree of antigenicity when tested in ELISA with IgG purified from HIV(+) broadly neutralizing sera while the production of synthetic peptides BS1 and BS2 failed due to their high degree of hydrophobicity. To overcome this limitation, we linked all four BS peptides to the COOH-terminus of GST protein to test both their antigenicity and immunogenicity. Only the BS1 peptide showed good antigenicity; however, no envelope specific antibodies were elicited upon mice immunization. Therefore we performed further analyses by linking BS1 peptide to the NH2-terminus of the E2 scaffold from the Geobacillus Stearothermophylus PDH complex. The E2-BS1 fusion peptide showed good antigenic results, however only one immunized rabbit elicited good antibody titers towards both the monomeric and oligomeric viral envelope glycoprotein (Env). In addition, moderate neutralizing antibodies response was elicited against two HIV-1 clade B and one clade C primary isolates. These preliminary data validate the peptide mimotope approach as a promising tool to obtain an effective HIV-1 vaccine.
authors: Department of Clinical and Experimental Medicine, University of Catanzaro "Magna Graecia", Catanzaro 88100, Italy.|Department of Biochemistry and Medical Biotechnology, University of Naples "Federico II", Naples 80131, Italy.
authors: Marco
authors: M
authors: Schiavone
authors: Department of Clinical and Experimental Medicine, University of Catanzaro "Magna Graecia", Catanzaro 88100, Italy.
authors: Giuseppe
authors: 0000-0002-5414-6190
authors: G
authors: Fiume
authors: IBP-CNR, Naples 80131, Italy.
authors: Antonella
authors: A
authors: Caivano
authors: Department of Clinical and Experimental Medicine, University of Catanzaro "Magna Graecia", Catanzaro 88100, Italy.
authors: Annamaria
authors: A
authors: De Laurentiis
authors: Department of Clinical and Experimental Medicine, University of Catanzaro "Magna Graecia", Catanzaro 88100, Italy.
authors: Cristina
authors: C
authors: Falcone
authors: Department of Clinical and Experimental Medicine, University of Catanzaro "Magna Graecia", Catanzaro 88100, Italy.
authors: Francesca Fasanella
authors: FF
authors: Masci
authors: Department of Clinical and Experimental Medicine, University of Catanzaro "Magna Graecia", Catanzaro 88100, Italy.
authors: Enrico
authors: 0000-0002-3565-7817
authors: E
authors: Iaccino
authors: Department of Clinical and Experimental Medicine, University of Catanzaro "Magna Graecia", Catanzaro 88100, Italy.
authors: Selena
authors: S
authors: Mimmi
authors: Department of Clinical and Experimental Medicine, University of Catanzaro "Magna Graecia", Catanzaro 88100, Italy.
authors: Camillo
authors: 0000-0001-6707-4723
authors: C
authors: Palmieri
authors: Department of Clinical and Experimental Medicine, University of Catanzaro "Magna Graecia", Catanzaro 88100, Italy.
authors: Antonio
authors: A
authors: Pisano
authors: Department of Clinical and Experimental Medicine, University of Catanzaro "Magna Graecia", Catanzaro 88100, Italy.
authors: Marilena
authors: M
authors: Pontoriero
authors: Department of Clinical and Experimental Medicine, University of Catanzaro "Magna Graecia", Catanzaro 88100, Italy.
authors: Annalisa
authors: A
authors: Rossi
authors: Department of Clinical and Experimental Medicine, University of Catanzaro "Magna Graecia", Catanzaro 88100, Italy.
authors: Annarita
authors: A
authors: Scialdone
authors: Department of Clinical and Experimental Medicine, University of Catanzaro "Magna Graecia", Catanzaro 88100, Italy.
authors: Eleonora
authors: 0000-0001-8422-2679
authors: E
authors: Vecchio
authors: Department of Chemistry, University of Naples "Federico II", Naples 80131, Italy.
authors: Concetta
authors: C
authors: Andreozzi
authors: IBP-CNR, Naples 80131, Italy.
authors: Maria
authors: M
authors: Trovato
authors: Research Institute of Animal Production, Nitra 94992, Slovakia.
authors: Jan
authors: J
authors: Rafay
authors: Institute of Applied Microbiology, Wien A-1190, Austria.
authors: Boris
authors: B
authors: Ferko
authors: Laboratory for AIDS Vaccine Research & Development, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
authors: David
authors: D
authors: Montefiori
authors: Department of Chemistry, University of Naples "Federico II", Naples 80131, Italy.
authors: Angela
authors: A
authors: Lombardi
authors: San Luigi AIDS Centre, San Raffaele Scientific Institute, Milan 20127, Italy.
authors: Giulia
authors: G
authors: Morsica
authors: San Luigi AIDS Centre, San Raffaele Scientific Institute, Milan 20127, Italy.|Division of Immunology, Transplantation and Infectious Diseases, Vita-Salute San Raffaele University School of Medicine, Milan 20132, Italy.
authors: Guido
authors: G
authors: Poli
authors: Department of Clinical and Experimental Medicine, University of Catanzaro "Magna Graecia", Catanzaro 88100, Italy.|Department of Biochemistry and Medical Biotechnology, University of Naples "Federico II", Naples 80131, Italy.
authors: Ileana
authors: 0000-0001-8212-8515
authors: I
authors: Quinto
authors: Department of Chemistry, University of Naples "Federico II", Naples 80131, Italy.
authors: Vincenzo
authors: V
authors: Pavone
authors: IBP-CNR, Naples 80131, Italy.
authors: Piergiuseppe
authors: P
authors: De Berardinis
authors: Department of Clinical and Experimental Medicine, University of Catanzaro "Magna Graecia", Catanzaro 88100, Italy.|Department of Biochemistry and Medical Biotechnology, University of Naples "Federico II", Naples 80131, Italy.
authors: Giuseppe
authors: G
authors: Scala
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000737:chemistry* / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D000939:Epitopes / Q000008:administration & dosage / Q000737:chemistry* / Q000276:immunology; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology*; D015497:HIV-1 / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry* / Q000276:immunology; D017434:Protein Structure, Tertiary; D011817:Rabbits; D016415:Sequence Alignment
chemical_list: D016915:AIDS Vaccines; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D010455:Peptides