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Immunogenicity of DNA Vaccines Encoding Simian Immunodeficiency Virus Antigen Targeted to Dendritic Cells in Rhesus Macaques

BACKGROUND: Targeting antigens encoded by DNA vaccines to dendritic cells (DCs) in the presence of adjuvants enhances their immunogenicity and efficacy in mice. METHODOLOGY/PRINCIPAL FINDINGS: To explore the immunogenicity of this approach in non-human primates, we generated a single chain antibody...

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Autores principales: Tenbusch, Matthias, Ignatius, Ralf, Nchinda, Godwin, Trumpfheller, Christine, Salazar, Andres M., Töpfer, Katharina, Sauermann, Ulrike, Wagner, Ralf, Hannaman, Drew, Tenner-Racz, Klara, Racz, Paul, Stahl-Hennig, Christiane, Überla, Klaus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3373620/
https://www.ncbi.nlm.nih.gov/pubmed/22720025
http://dx.doi.org/10.1371/journal.pone.0039038
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author Tenbusch, Matthias
Ignatius, Ralf
Nchinda, Godwin
Trumpfheller, Christine
Salazar, Andres M.
Töpfer, Katharina
Sauermann, Ulrike
Wagner, Ralf
Hannaman, Drew
Tenner-Racz, Klara
Racz, Paul
Stahl-Hennig, Christiane
Überla, Klaus
author_facet Tenbusch, Matthias
Ignatius, Ralf
Nchinda, Godwin
Trumpfheller, Christine
Salazar, Andres M.
Töpfer, Katharina
Sauermann, Ulrike
Wagner, Ralf
Hannaman, Drew
Tenner-Racz, Klara
Racz, Paul
Stahl-Hennig, Christiane
Überla, Klaus
author_sort Tenbusch, Matthias
collection PubMed
description BACKGROUND: Targeting antigens encoded by DNA vaccines to dendritic cells (DCs) in the presence of adjuvants enhances their immunogenicity and efficacy in mice. METHODOLOGY/PRINCIPAL FINDINGS: To explore the immunogenicity of this approach in non-human primates, we generated a single chain antibody to the antigen uptake receptor DEC-205 expressed on rhesus macaque DCs. DNA vaccines encoding this single chain antibody fused to the SIV capsid protein were delivered to six monkeys each by either intramuscular electroporation or conventional intramuscular injection co-injected or not with poly ICLC, a stabilized poly I: C analogue, as adjuvant. Antibodies to capsid were induced by the DC-targeting and non-targeting control DNA delivered by electroporation while conventional DNA immunization at a 10-fold higher dose of DNA failed to induce detectable humoral immune responses. Substantial cellular immune responses were also observed after DNA electroporation of both DNAs, but stronger responses were induced by the non-targeting vaccine. Conventional immunization with the DC-targeting DNA at a 10-fold higher dose did not give rise to substantial cellular immune responses, neither when co-injected with poly ICLC. CONCLUSIONS/SIGNIFICANCE: The study confirms the potent immunogenicity of DNA vaccines delivered by electroporation. Targeting the DNA via a single chain antibody to DEC-205 expressed by DCs, however, does not improve the immunogenicity of the antigens in non-human primates.
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spelling pubmed-33736202012-06-20 Immunogenicity of DNA Vaccines Encoding Simian Immunodeficiency Virus Antigen Targeted to Dendritic Cells in Rhesus Macaques Tenbusch, Matthias Ignatius, Ralf Nchinda, Godwin Trumpfheller, Christine Salazar, Andres M. Töpfer, Katharina Sauermann, Ulrike Wagner, Ralf Hannaman, Drew Tenner-Racz, Klara Racz, Paul Stahl-Hennig, Christiane Überla, Klaus PLoS One Research Article BACKGROUND: Targeting antigens encoded by DNA vaccines to dendritic cells (DCs) in the presence of adjuvants enhances their immunogenicity and efficacy in mice. METHODOLOGY/PRINCIPAL FINDINGS: To explore the immunogenicity of this approach in non-human primates, we generated a single chain antibody to the antigen uptake receptor DEC-205 expressed on rhesus macaque DCs. DNA vaccines encoding this single chain antibody fused to the SIV capsid protein were delivered to six monkeys each by either intramuscular electroporation or conventional intramuscular injection co-injected or not with poly ICLC, a stabilized poly I: C analogue, as adjuvant. Antibodies to capsid were induced by the DC-targeting and non-targeting control DNA delivered by electroporation while conventional DNA immunization at a 10-fold higher dose of DNA failed to induce detectable humoral immune responses. Substantial cellular immune responses were also observed after DNA electroporation of both DNAs, but stronger responses were induced by the non-targeting vaccine. Conventional immunization with the DC-targeting DNA at a 10-fold higher dose did not give rise to substantial cellular immune responses, neither when co-injected with poly ICLC. CONCLUSIONS/SIGNIFICANCE: The study confirms the potent immunogenicity of DNA vaccines delivered by electroporation. Targeting the DNA via a single chain antibody to DEC-205 expressed by DCs, however, does not improve the immunogenicity of the antigens in non-human primates. Public Library of Science 2012-06-12 /pmc/articles/PMC3373620/ /pubmed/22720025 http://dx.doi.org/10.1371/journal.pone.0039038 Text en Tenbusch et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Tenbusch, Matthias
Ignatius, Ralf
Nchinda, Godwin
Trumpfheller, Christine
Salazar, Andres M.
Töpfer, Katharina
Sauermann, Ulrike
Wagner, Ralf
Hannaman, Drew
Tenner-Racz, Klara
Racz, Paul
Stahl-Hennig, Christiane
Überla, Klaus
Immunogenicity of DNA Vaccines Encoding Simian Immunodeficiency Virus Antigen Targeted to Dendritic Cells in Rhesus Macaques
title Immunogenicity of DNA Vaccines Encoding Simian Immunodeficiency Virus Antigen Targeted to Dendritic Cells in Rhesus Macaques
title_full Immunogenicity of DNA Vaccines Encoding Simian Immunodeficiency Virus Antigen Targeted to Dendritic Cells in Rhesus Macaques
title_fullStr Immunogenicity of DNA Vaccines Encoding Simian Immunodeficiency Virus Antigen Targeted to Dendritic Cells in Rhesus Macaques
title_full_unstemmed Immunogenicity of DNA Vaccines Encoding Simian Immunodeficiency Virus Antigen Targeted to Dendritic Cells in Rhesus Macaques
title_short Immunogenicity of DNA Vaccines Encoding Simian Immunodeficiency Virus Antigen Targeted to Dendritic Cells in Rhesus Macaques
title_sort immunogenicity of dna vaccines encoding simian immunodeficiency virus antigen targeted to dendritic cells in rhesus macaques
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3373620/
https://www.ncbi.nlm.nih.gov/pubmed/22720025
http://dx.doi.org/10.1371/journal.pone.0039038
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