Negatively charged glyconanoparticles modulate and stabilize the secondary structures of a gp120 V3 loop peptide: toward fully synthetic HIV vaccine candidates.
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.
‡CIBER-BBN, P° de Miramón 182, 20009 San Sebastian, Spain.
Paolo Di
PD
Gianvincenzo
Javier
J
Calvo
∥Département de Pharmacochimie, UMR 5063 CNRS-Université Grenoble Alpes, BP53, 38041, Grenoble cédex 09, France.
Serge
S
Perez
⊥Aids Immunopathology Unit, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Ctra Pozuelo Km. 2, 28220, Majadahonda, Madrid, Spain.
Amparo
A
Álvarez
⊥Aids Immunopathology Unit, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Ctra Pozuelo Km. 2, 28220, Majadahonda, Madrid, Spain.|#Pharmacology Department, Pharmacy Faculty, Universidad Complutense de Madrid. Pz. Ramón Y Cajal, 28040, Madrid, Spain.
Luis Miguel
LM
Bedoya
⊥Aids Immunopathology Unit, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Ctra Pozuelo Km. 2, 28220, Majadahonda, Madrid, Spain.
José
J
Alcamí
‡CIBER-BBN, P° de Miramón 182, 20009 San Sebastian, Spain.
Soledad
S
Penadés
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000096:biosynthesis / Q000737:chemistry* / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D057134:Antibodies, Neutralizing / Q000737:chemistry; D000914:Antibodies, Viral / Q000096:biosynthesis*; D005260:Female; D006046:Gold / Q000737:chemistry; D015699:HIV Envelope Protein gp120 / Q000819:agonists / Q000737:chemistry / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D053758:Nanoparticles / Q000737:chemistry*; D009500:Neutralization Tests; D055550:Protein Stability; D017433:Protein Structure, Secondary; D011817:Rabbits; D055672:Static Electricity; D014614:Vaccines, Synthetic
D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015699:HIV Envelope Protein gp120; D018796:Immunoconjugates; D014614:Vaccines, Synthetic; D006046:Gold