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Attenuation of Replication-Competent Adenovirus Serotype 26 Vaccines by Vectorization

Replication-competent adenovirus (rcAd)-based vaccine vectors may theoretically provide immunological advantages over replication-incompetent Ad vectors, but they also raise additional potential clinical and regulatory issues. We produced replication-competent Ad serotype 26 (rcAd26) vectors by addi...

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Autores principales: Maxfield, Lori F., Abbink, Peter, Stephenson, Kathryn E., Borducchi, Erica N., Ng'ang'a, David, Kirilova, Marinela M., Paulino, Noelix, Boyd, Michael, Shabram, Paul, Ruan, Qian, Patel, Mayank, Barouch, Dan H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4622110/
https://www.ncbi.nlm.nih.gov/pubmed/26376928
http://dx.doi.org/10.1128/CVI.00510-15
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author Maxfield, Lori F.
Abbink, Peter
Stephenson, Kathryn E.
Borducchi, Erica N.
Ng'ang'a, David
Kirilova, Marinela M.
Paulino, Noelix
Boyd, Michael
Shabram, Paul
Ruan, Qian
Patel, Mayank
Barouch, Dan H.
author_facet Maxfield, Lori F.
Abbink, Peter
Stephenson, Kathryn E.
Borducchi, Erica N.
Ng'ang'a, David
Kirilova, Marinela M.
Paulino, Noelix
Boyd, Michael
Shabram, Paul
Ruan, Qian
Patel, Mayank
Barouch, Dan H.
author_sort Maxfield, Lori F.
collection PubMed
description Replication-competent adenovirus (rcAd)-based vaccine vectors may theoretically provide immunological advantages over replication-incompetent Ad vectors, but they also raise additional potential clinical and regulatory issues. We produced replication-competent Ad serotype 26 (rcAd26) vectors by adding the E1 region back into a replication-incompetent Ad26 vector backbone with the E3 or E3/E4 regions deleted. We assessed the effect of vectorization on the replicative capacity of the rcAd26 vaccines. Attenuation occurred in a stepwise fashion, with E3 deletion, E4 deletion, and human immunodeficiency virus type 1 (HIV-1) envelope (Env) gene insertion all contributing to reduced replicative capacity compared to that with the wild-type Ad26 vector. The rcAd26 vector with E3 and E4 deleted and containing the Env transgene exhibited 2.7- to 4.4-log-lower replicative capacity than that of the wild-type Ad26 in vitro. This rcAd26 vector is currently being evaluated in a phase 1 clinical trial. Attenuation as a result of vectorization and transgene insertion has implications for the clinical development of replication-competent vaccine vectors.
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spelling pubmed-46221102015-11-09 Attenuation of Replication-Competent Adenovirus Serotype 26 Vaccines by Vectorization Maxfield, Lori F. Abbink, Peter Stephenson, Kathryn E. Borducchi, Erica N. Ng'ang'a, David Kirilova, Marinela M. Paulino, Noelix Boyd, Michael Shabram, Paul Ruan, Qian Patel, Mayank Barouch, Dan H. Clin Vaccine Immunol Vaccines Replication-competent adenovirus (rcAd)-based vaccine vectors may theoretically provide immunological advantages over replication-incompetent Ad vectors, but they also raise additional potential clinical and regulatory issues. We produced replication-competent Ad serotype 26 (rcAd26) vectors by adding the E1 region back into a replication-incompetent Ad26 vector backbone with the E3 or E3/E4 regions deleted. We assessed the effect of vectorization on the replicative capacity of the rcAd26 vaccines. Attenuation occurred in a stepwise fashion, with E3 deletion, E4 deletion, and human immunodeficiency virus type 1 (HIV-1) envelope (Env) gene insertion all contributing to reduced replicative capacity compared to that with the wild-type Ad26 vector. The rcAd26 vector with E3 and E4 deleted and containing the Env transgene exhibited 2.7- to 4.4-log-lower replicative capacity than that of the wild-type Ad26 in vitro. This rcAd26 vector is currently being evaluated in a phase 1 clinical trial. Attenuation as a result of vectorization and transgene insertion has implications for the clinical development of replication-competent vaccine vectors. American Society for Microbiology 2015-10-26 2015-11 /pmc/articles/PMC4622110/ /pubmed/26376928 http://dx.doi.org/10.1128/CVI.00510-15 Text en Copyright © 2015, Maxfield et al. http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0/) , which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Vaccines
Maxfield, Lori F.
Abbink, Peter
Stephenson, Kathryn E.
Borducchi, Erica N.
Ng'ang'a, David
Kirilova, Marinela M.
Paulino, Noelix
Boyd, Michael
Shabram, Paul
Ruan, Qian
Patel, Mayank
Barouch, Dan H.
Attenuation of Replication-Competent Adenovirus Serotype 26 Vaccines by Vectorization
title Attenuation of Replication-Competent Adenovirus Serotype 26 Vaccines by Vectorization
title_full Attenuation of Replication-Competent Adenovirus Serotype 26 Vaccines by Vectorization
title_fullStr Attenuation of Replication-Competent Adenovirus Serotype 26 Vaccines by Vectorization
title_full_unstemmed Attenuation of Replication-Competent Adenovirus Serotype 26 Vaccines by Vectorization
title_short Attenuation of Replication-Competent Adenovirus Serotype 26 Vaccines by Vectorization
title_sort attenuation of replication-competent adenovirus serotype 26 vaccines by vectorization
topic Vaccines
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4622110/
https://www.ncbi.nlm.nih.gov/pubmed/26376928
http://dx.doi.org/10.1128/CVI.00510-15
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