Abstract
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 (in vivo) 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 via 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 1H NMR spectroscopy. Then, the G4-PAMAM-peptide complexes were assayed in vivo 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) via increase in IgG and IgA, respectively. This demonstrated that G4-PAMAM can be used as a nanocarrier for immunogenic peptides.