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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Main Authors: Matthias Tenbusch, Ralf Ignatius, Godwin Nchinda, Christine Trumpfheller, Andres M Salazar, Katharina Töpfer, Ulrike Sauermann, Ralf Wagner, Drew Hannaman, Klara Tenner-Racz, Paul Racz, Christiane Stahl-Hennig, Klaus Uberla
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3373620?pdf=render
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spelling doaj-90c324a3d00d4e3d9c038fc5a655ed732020-11-25T01:53:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0176e3903810.1371/journal.pone.0039038Immunogenicity of DNA vaccines encoding simian immunodeficiency virus antigen targeted to dendritic cells in rhesus macaques.Matthias TenbuschRalf IgnatiusGodwin NchindaChristine TrumpfhellerAndres M SalazarKatharina TöpferUlrike SauermannRalf WagnerDrew HannamanKlara Tenner-RaczPaul RaczChristiane Stahl-HennigKlaus UberlaBACKGROUND: 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.http://europepmc.org/articles/PMC3373620?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Matthias Tenbusch
Ralf Ignatius
Godwin Nchinda
Christine Trumpfheller
Andres M Salazar
Katharina Töpfer
Ulrike Sauermann
Ralf Wagner
Drew Hannaman
Klara Tenner-Racz
Paul Racz
Christiane Stahl-Hennig
Klaus Uberla
spellingShingle Matthias Tenbusch
Ralf Ignatius
Godwin Nchinda
Christine Trumpfheller
Andres M Salazar
Katharina Töpfer
Ulrike Sauermann
Ralf Wagner
Drew Hannaman
Klara Tenner-Racz
Paul Racz
Christiane Stahl-Hennig
Klaus Uberla
Immunogenicity of DNA vaccines encoding simian immunodeficiency virus antigen targeted to dendritic cells in rhesus macaques.
PLoS ONE
author_facet Matthias Tenbusch
Ralf Ignatius
Godwin Nchinda
Christine Trumpfheller
Andres M Salazar
Katharina Töpfer
Ulrike Sauermann
Ralf Wagner
Drew Hannaman
Klara Tenner-Racz
Paul Racz
Christiane Stahl-Hennig
Klaus Uberla
author_sort Matthias Tenbusch
title 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_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_sort immunogenicity of dna vaccines encoding simian immunodeficiency virus antigen targeted to dendritic cells in rhesus macaques.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2012-01-01
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.
url http://europepmc.org/articles/PMC3373620?pdf=render
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