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In silico search, chemical characterization and immunogenic evaluation of amino-terminated G4-PAMAM-HIV peptide complexes using three-dimensional models of the HIV-1 gp120 protein.
In silico search, chemical characterization and immunogenic evaluation of amino-terminated G4-PAMAM-HIV peptide complexes using three-dimensional models of the HIV-1 gp120 protein.
- Source :
-
Colloids and surfaces. B, Biointerfaces [Colloids Surf B Biointerfaces] 2019 May 01; Vol. 177, pp. 77-93. Date of Electronic Publication: 2019 Jan 18. - Publication Year :
- 2019
-
Abstract
- Peptide epitopes have been widely used to develop synthetic vaccines and immunotherapies. However, peptide epitopes may exhibit poor absorption or immunogenicity due to their low molecular weights. Conversely, fourth-generation polyamidoamine (G4-PAMAM) dendrimers are nonimmunogenic and relatively nontoxic synthetic nanoparticles that have been used as adjuvants and nanocarriers of small peptides and to improve nasal absorption. Based on this information, we hypothesized that the combination of intranasal immunization and G4-PAMAM dendrimers would be useful for enhancing the antibody responses of HIV-1 gp120 peptide epitopes. Therefore, we first used structural data, peptide epitope predictors and docking and MD simulations on MHC-II to identify two peptide epitopes on the CD4 binding site of HIV-1 gp120. The formation of G4-PAMAM-peptide complexes was evaluated in silico (molecular docking studies using different G4-PAMAM conformations retrieved from MD simulations as well as the MMGBSA approach) and validated experimentally (electrophoresis, <superscript>1</superscript> H NMR and cryo-TEM). Next, the G4-PAMAM dendrimer-peptide complexes were administered intranasally to groups of female BALB/cJ mice. The results showed that both peptides were immunogenic at the systemic and mucosal levels (nasal and vaginal), and G4-PAMAM dendrimer-peptide complexes improved IgG and IgA responses in serum and nasal washes. Thus, G4-PAMAM dendrimers have potential for use as adjuvants and nanocarriers of peptides.<br /> (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Female
HIV Envelope Protein gp120 genetics
HIV Envelope Protein gp120 immunology
Mice
Mice, Inbred BALB C
Peptides genetics
Computer Simulation
Dendrimers chemistry
HIV Envelope Protein gp120 chemistry
HIV-1 chemistry
HIV-1 immunology
Models, Molecular
Nylons chemistry
Peptides chemistry
Peptides immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-4367
- Volume :
- 177
- Database :
- MEDLINE
- Journal :
- Colloids and surfaces. B, Biointerfaces
- Publication Type :
- Academic Journal
- Accession number :
- 30711762
- Full Text :
- https://doi.org/10.1016/j.colsurfb.2019.01.034