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Int. J. Mol. Sci. 2012, 13(5), 5674-5699; doi:10.3390/ijms13055674
Article

Design and Characterization of a Peptide Mimotope of the HIV-1 gp120 Bridging Sheet

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Received: 19 April 2012; in revised form: 26 April 2012 / Accepted: 2 May 2012 / Published: 10 May 2012
(This article belongs to the Special Issue Advances in Molecular Immunology)
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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 HIV-1 vaccine; bridging sheet; mimotope
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

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.

AMA Style

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.

Chicago/Turabian Style

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.


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