Design and characterization of a peptide mimotope of the HIV-1 gp120 bridging sheet

Marco Schiavone, Giuseppe Fiume, Antonella Caivano, Annamaria de Laurentiis, Cristina Falcone, Francesca Fasanella Masci, Enrico Iaccino, Selena Mimmi, Camillo Palmieri, Antonio Pisano, Marilena Pontoriero, Annalisa Rossi, Annarita Scialdone, Eleonora Vecchio, Concetta Andreozzi, Maria Trovato, Jan Rafay, Boris Ferko, David Montefiori, Angela LombardiGiulia Morsica, Guido Poli, Ileana Quinto, Vincenzo Pavone, Piergiuseppe de Berardinis, Giuseppe Scala

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)5674-5699
Number of pages26
JournalInternational Journal of Molecular Sciences
Volume13
Issue number5
DOIs
Publication statusPublished - May 2012

Keywords

  • Bridging sheet
  • HIV-1 vaccine
  • Mimotope

ASJC Scopus subject areas

  • Computer Science Applications
  • Molecular Biology
  • Catalysis
  • Inorganic Chemistry
  • Spectroscopy
  • Organic Chemistry
  • Physical and Theoretical Chemistry
  • Medicine(all)

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