In silico and in vivo studies of gp120-HIV-derived peptides in complex with G4-PAMAM dendrimers

Novel synthetic vaccines as immunotherapy approaches for HIV are interesting strategies that imply big challenges as they increase the poor immunogenic properties of peptide epitopes and their structural damage from the physiological environment. In this work, we used fourth-generation polyamidoamin...

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Bibliographic Details
Published in:RSC advances 2020-05, Vol.10 (35), p.20414-20426
Main Authors: Rolando Alberto, Rodríguez-Fonseca, Martiniano, Bello, Saúl, Rojas-Hernández, Jazmín, García-Machorro, Mara, Gutiérrez-Sánchez, Alan Rubén, Estrada-Pérez, Manuel Jonathan, Fragoso-Vázquez, Juan Vicente, Méndez-Méndez, José, Correa-Basurto
Format: Article
Language:English
Subjects:
Antibodies
Atomic force microscopy
Chemistry
Dendrimers
In vivo methods and tests
Molecular dynamics
NMR spectroscopy
Peptides
Structural damage
Vaccines
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Summary:Novel synthetic vaccines as immunotherapy approaches for HIV are interesting strategies that imply big challenges as they increase the poor immunogenic properties of peptide epitopes and their structural damage from the physiological environment. In this work, we used fourth-generation polyamidoamine dendrimers (G4-PAMAM) to increase the immunoglobulin responses ( ) induced by two peptide epitopes (pPGT122: DIIGDIRQAH and pVRC03: DGGANNTSNETFR), both recognized by broadly neutralizing antibodies (bNAb) on gp120-HIV type 1. pPGT122 and pVRC03 were identified on the gp120 surface recognition by bNAb by using X-ray diffraction-derived structures obtained from the Protein Data Bank. pPGT122 and pVRC03 were coupled to the G4-PAMAM molecule by ligand diffusion using molecular dynamics (LDMDS) simulations and their energetic values were calculated by using the MMGBSA approach. Additionally, docking and MD simulations showed the affinity of pPGT122 and pVRC03 for MHC-I/II. G4-PAMAM-peptide complexes were chemically characterized through MALDI-TOF-MS, LC-ESI-QTOF-MS, atomic force microscopy (AFM) and H NMR spectroscopy. Then, the G4-PAMAM-peptide complexes were assayed by intranasal administration in female BALB/cJ mouse groups, showing that both peptides were immunogenic systemically and in the mucous membrane (in nasal and vaginal washes) increase in IgG and IgA, respectively. This demonstrated that G4-PAMAM can be used as a nanocarrier for immunogenic peptides.
ISSN:2046-2069
2046-2069
DOI:10.1039/d0ra00840k