Enhancement of Immune Responses by Guanosine-Based Particles in DNA Plasmid Formulations against Infectious Diseases

Immunogenicity of DNA vaccines can be efficiently improved by adding adjuvants into their formulations. In this regard, the application of nano- and microparticles as vaccines adjuvants, or delivery systems, provides a powerful tool in designing modern vaccines. In the present study, we examined the...

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Main Authors: Saritza Santos, Maité Ramírez, Eric Miranda, Nelson Reyes, Osmarie Martínez, Maxier Acosta-Santiago, José M. Rivera, Miguel Otero
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2019/3409371
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author Saritza Santos
Maité Ramírez
Eric Miranda
Nelson Reyes
Osmarie Martínez
Maxier Acosta-Santiago
José M. Rivera
Miguel Otero
author_facet Saritza Santos
Maité Ramírez
Eric Miranda
Nelson Reyes
Osmarie Martínez
Maxier Acosta-Santiago
José M. Rivera
Miguel Otero
author_sort Saritza Santos
collection DOAJ
description Immunogenicity of DNA vaccines can be efficiently improved by adding adjuvants into their formulations. In this regard, the application of nano- and microparticles as vaccines adjuvants, or delivery systems, provides a powerful tool in designing modern vaccines. In the present study, we examined the role of “Supramolecular Hacky Sacks” (SHS) particles, made via the hierarchical self-assembly of a guanosine derivative, as a novel immunomodulator for DNA plasmid preparations. These plasmids code for the proteins HIV-1 Gag (pGag), the wild-type vaccinia virus Western Reserve A27 (pA27L), or a codon-optimized version of the latter (pOD1A27Lopt), which is also linked to the sequence of the outer domain-1 (OD1) from HIV-1 gp120 protein. We evaluated the enhancement of the immune responses generated by our DNA plasmid formulations in a murine model through ELISpot and ELISA assays. The SHS particles increased the frequencies of IFN-γ-producing cells in mice independently immunized with pGag and pA27L plasmids. Moreover, the addition of SHS to pGag and pA27L DNA plasmid formulations enhanced the production of IFN-γ (Th1-type) over IL-4 (Th2-type) cellular immune responses. Furthermore, pGag and pA27L plasmids formulated with SHS, triggered the production of antigen-specific IgG in mice, especially the IgG2a isotype. However, no improvement of either of those adaptive immune responses was observed in mice receiving pOD1A27Lopt+SHS. Here, we demonstrated that SHS particles have the ability to improve both arms of adaptive immunity of plasmid coding “wild-type” antigens without additional strategies to boost their immunogenicity. To the best of our knowledge, this is the first report of SHS guanosine-based particles as DNA plasmid adjuvants.
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spelling doaj-art-a27d43722e224572a3493d9aff07cbf52025-08-20T02:20:19ZengWileyJournal of Immunology Research2314-88612314-71562019-01-01201910.1155/2019/34093713409371Enhancement of Immune Responses by Guanosine-Based Particles in DNA Plasmid Formulations against Infectious DiseasesSaritza Santos0Maité Ramírez1Eric Miranda2Nelson Reyes3Osmarie Martínez4Maxier Acosta-Santiago5José M. Rivera6Miguel Otero7Department of Microbiology and Medical Zoology, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico, USADepartment of Microbiology and Medical Zoology, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico, USADepartment of Microbiology and Medical Zoology, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico, USASchool of Science and Technology, Universidad del Este, Carolina, Puerto Rico, USADepartment of Microbiology and Medical Zoology, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico, USADepartment of Chemistry, University of Puerto Rico, Rio Piedras Campus, San Juan, Puerto Rico, USADepartment of Chemistry, University of Puerto Rico, Rio Piedras Campus, San Juan, Puerto Rico, USADepartment of Microbiology and Medical Zoology, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico, USAImmunogenicity of DNA vaccines can be efficiently improved by adding adjuvants into their formulations. In this regard, the application of nano- and microparticles as vaccines adjuvants, or delivery systems, provides a powerful tool in designing modern vaccines. In the present study, we examined the role of “Supramolecular Hacky Sacks” (SHS) particles, made via the hierarchical self-assembly of a guanosine derivative, as a novel immunomodulator for DNA plasmid preparations. These plasmids code for the proteins HIV-1 Gag (pGag), the wild-type vaccinia virus Western Reserve A27 (pA27L), or a codon-optimized version of the latter (pOD1A27Lopt), which is also linked to the sequence of the outer domain-1 (OD1) from HIV-1 gp120 protein. We evaluated the enhancement of the immune responses generated by our DNA plasmid formulations in a murine model through ELISpot and ELISA assays. The SHS particles increased the frequencies of IFN-γ-producing cells in mice independently immunized with pGag and pA27L plasmids. Moreover, the addition of SHS to pGag and pA27L DNA plasmid formulations enhanced the production of IFN-γ (Th1-type) over IL-4 (Th2-type) cellular immune responses. Furthermore, pGag and pA27L plasmids formulated with SHS, triggered the production of antigen-specific IgG in mice, especially the IgG2a isotype. However, no improvement of either of those adaptive immune responses was observed in mice receiving pOD1A27Lopt+SHS. Here, we demonstrated that SHS particles have the ability to improve both arms of adaptive immunity of plasmid coding “wild-type” antigens without additional strategies to boost their immunogenicity. To the best of our knowledge, this is the first report of SHS guanosine-based particles as DNA plasmid adjuvants.http://dx.doi.org/10.1155/2019/3409371
spellingShingle Saritza Santos
Maité Ramírez
Eric Miranda
Nelson Reyes
Osmarie Martínez
Maxier Acosta-Santiago
José M. Rivera
Miguel Otero
Enhancement of Immune Responses by Guanosine-Based Particles in DNA Plasmid Formulations against Infectious Diseases
Journal of Immunology Research
title Enhancement of Immune Responses by Guanosine-Based Particles in DNA Plasmid Formulations against Infectious Diseases
title_full Enhancement of Immune Responses by Guanosine-Based Particles in DNA Plasmid Formulations against Infectious Diseases
title_fullStr Enhancement of Immune Responses by Guanosine-Based Particles in DNA Plasmid Formulations against Infectious Diseases
title_full_unstemmed Enhancement of Immune Responses by Guanosine-Based Particles in DNA Plasmid Formulations against Infectious Diseases
title_short Enhancement of Immune Responses by Guanosine-Based Particles in DNA Plasmid Formulations against Infectious Diseases
title_sort enhancement of immune responses by guanosine based particles in dna plasmid formulations against infectious diseases
url http://dx.doi.org/10.1155/2019/3409371
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