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Design and Characterization of a Peptide Mimotope of the HIV-1 gp120 Bridging Sheet
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
IBP-CNR, Naples 80131, Italy
Department of Chemistry, University of Naples “Federico II”, Naples 80131, Italy
Research Institute of Animal Production, Nitra 94992, Slovakia
Institute of Applied Microbiology, Wien A-1190, Austria
Laboratory for AIDS Vaccine Research & Development, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
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
These authors contributed equally to this work.
Present address: Department of Biology, Biology Building “Vallisneri”, University of Padua, Padua 35131, Italy.
Present address: Molecular Oncology Unit, Department of Oncoematology, IRCCS, “C.R.O.B.”, Rionero in Vulture, Potenza 85028, Italy.
* Authors to whom correspondence should be addressed.
Received: 19 April 2012; in revised form: 26 April 2012 / Accepted: 2 May 2012 / Published: 10 May 2012
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.
Keywords: HIV-1 vaccine; bridging sheet; mimotope
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Schiavone, M.; Fiume, G.; Caivano, A.; de Laurentiis, A.; Falcone, C.; Masci, F.F.; Iaccino, E.; Mimmi, S.; Palmieri, C.; Pisano, A.; Pontoriero, M.; Rossi, A.; Scialdone, A.; Vecchio, E.; Andreozzi, C.; Trovato, M.; Rafay, J.; Ferko, B.; Montefiori, D.; Lombardi, A.; Morsica, G.; Poli, G.; Quinto, I.; Pavone, V.; de Berardinis, P.; Scala, G. Design and Characterization of a Peptide Mimotope of the HIV-1 gp120 Bridging Sheet. Int. J. Mol. Sci. 2012, 13, 5674-5699.
Schiavone M, Fiume G, Caivano A, de Laurentiis A, Falcone C, Masci FF, Iaccino E, Mimmi S, Palmieri C, Pisano A, Pontoriero M, Rossi A, Scialdone A, Vecchio E, Andreozzi C, Trovato M, Rafay J, Ferko B, Montefiori D, Lombardi A, Morsica G, Poli G, Quinto I, Pavone V, de Berardinis P, Scala G. Design and Characterization of a Peptide Mimotope of the HIV-1 gp120 Bridging Sheet. International Journal of Molecular Sciences. 2012; 13(5):5674-5699.
Schiavone, Marco; Fiume, Giuseppe; Caivano, Antonella; de Laurentiis, Annamaria; Falcone, Cristina; Masci, Francesca Fasanella; Iaccino, Enrico; Mimmi, Selena; Palmieri, Camillo; Pisano, Antonio; Pontoriero, Marilena; Rossi, Annalisa; Scialdone, Annarita; Vecchio, Eleonora; Andreozzi, Concetta; Trovato, Maria; Rafay, Jan; Ferko, Boris; Montefiori, David; Lombardi, Angela; Morsica, Giulia; Poli, Guido; Quinto, Ileana; Pavone, Vincenzo; de Berardinis, Piergiuseppe; Scala, Giuseppe. 2012. "Design and Characterization of a Peptide Mimotope of the HIV-1 gp120 Bridging Sheet." Int. J. Mol. Sci. 13, no. 5: 5674-5699.