Next Article in Journal
Development of Nine Markers and Characterization of the Microsatellite Loci in the Endangered Gymnogobius isaza (Gobiidae)
Next Article in Special Issue
WIP Remodeling Actin behind the Scenes: How WIP Reshapes Immune and Other Functions
Previous Article in Journal
Comparison of Standard 1.5 T vs. 3 T Optimized Protocols in Patients Treated with Glatiramer Acetate. A Serial MRI Pilot Study
Previous Article in Special Issue
Modification of MCF-10A Cells with Pioglitazone and Serum-Rich Growth Medium Increases Soluble Factors in the Conditioned Medium, Likely Reducing BT-474 Cell Growth
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

1,2,†,††,* , 1,†,* , 3,§, 1
, 1
, 1
, 1
, 1
, 1
, 1
, 1
, 1
, 1
, 1
, 4
, 3
, 5
, 6
, 7
, 4
, 8
, 8,9
, 1,2,* , 4
, 3
 and 1,2,*
1 Department of Clinical and Experimental Medicine, University of Catanzaro “Magna Graecia”, Catanzaro 88100, Italy 2 Department of Biochemistry and Medical Biotechnology, University of Naples “Federico II”, Naples 80131, Italy 3 IBP-CNR, Naples 80131, Italy 4 Department of Chemistry, University of Naples “Federico II”, Naples 80131, Italy 5 Research Institute of Animal Production, Nitra 94992, Slovakia 6 Institute of Applied Microbiology, Wien A-1190, Austria 7 Laboratory for AIDS Vaccine Research & Development, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA 8 San Luigi AIDS Centre, San Raffaele Scientific Institute, Milan 20127, Italy 9 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 / Revised: 26 April 2012 / Accepted: 2 May 2012 / Published: 10 May 2012
(This article belongs to the Special Issue Advances in Molecular Immunology)
View Full-Text   |   Download PDF [635 KB, uploaded 19 June 2014]   |   Browse Figures

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.

Share & Cite This Article

Export to BibTeX |
EndNote


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.

View more citation formats

Related Articles

Article Metrics

Comments

Citing Articles

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert