Negatively charged glyconanoparticles modulate and stabilize the secondary structures of a gp120 V3 loop peptide: toward fully synthetic HIV vaccine candidates

Bioconjugate Chemistry
Paolo Di GianvincenzoSoledad Penadés

Abstract

The third variable region (V3 peptide) of the HIV-1 gp120 is a major immunogenic domain of HIV-1. Controlling the formation of the immunologically active conformation is a crucial step to the rational design of fully synthetic candidate vaccines. Herein, we present the modulation and stabilization of either the α-helix or β-strand conformation of the V3 peptide by conjugation to negatively charged gold glyconanoparticles (GNPs). The formation of the secondary structure can be triggered by the variation of the buffer concentration and/or pH as indicated by circular dichoism. The peptide on the GNPs shows increased stability toward peptidase degradation as compared to the free peptide. Moreover, only the V3β-GNPs bind to the anti-V3 human broadly neutralizing mAb 447-52D as demonstrated by surface plasmon resonance (SPR). The strong binding of V3β-GNPs to the 447-52D mAb was the starting point to address its study as immunogen. V3β-GNPs elicit antibodies in rabbits that recognize a recombinant gp120 and the serum displayed low but consistent neutralizing activity. These results open up the way for the design of new fully synthetic HIV vaccine candidates.

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Citations

Aug 8, 2015·Human Vaccines & Immunotherapeutics·Ricardo Calderon-GonzalezCarmen Alvarez-Dominguez
Apr 23, 2016·Vaccines·Abhishek Vartak, Steven J Sucheck
May 23, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sónia Alexandra Correia Carabineiro
Feb 27, 2018·Chemical Society Reviews·Christopher D SpicerMolly M Stevens
Jul 8, 2017·Beilstein Journal of Organic Chemistry·Federica CompostellaLaura Polito
Apr 30, 2017·Chemical Science·Lev A Dykman, Nikolai G Khlebtsov
Jul 28, 2020·Nanomaterials·Filip KvetonJan Tkac
Jul 5, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Eva Torres-SangiaoMonica Cartelle Gestal
Jan 27, 2019·Journal of Peptide Science : an Official Publication of the European Peptide Society·I GuryanovT Tennikova
Feb 3, 2021·Critical Reviews in Biotechnology·Akhilesh Rai, Lino Ferreira
Jan 22, 2021·Langmuir : the ACS Journal of Surfaces and Colloids·Zuzana GaraiovaMaria Bryszewska
Feb 19, 2021·APL Bioengineering·Sushma Kumari, Kaushik Chatterjee
Apr 16, 2020·Nano Today·Krystina L HessChristopher M Jewell

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