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Ebola-GP DNA Prime rAd5-GP Boost: Influence of Prime Frequency and Prime/Boost Time Interval on the Immune Response in Non-human Primates

Heterologous prime-boost immunization regimens are a common strategy for many vaccines. DNA prime rAd5-GP boost immunization has been demonstrated to protect non-human primates against a lethal challenge of Ebola virus, a pathogen that causes fatal hemorrhagic disease in humans. This protection corr...

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Autores principales: Marcus, Hadar, Thompson, Emily, Zhou, Yan, Bailey, Michael, Donaldson, Mitzi M., Stanley, Daphne A., Asiedu, Clement, Foulds, Kathryn E., Roederer, Mario, Moliva, Juan I., Sullivan, Nancy J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006325/
https://www.ncbi.nlm.nih.gov/pubmed/33790899
http://dx.doi.org/10.3389/fimmu.2021.627688
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author Marcus, Hadar
Thompson, Emily
Zhou, Yan
Bailey, Michael
Donaldson, Mitzi M.
Stanley, Daphne A.
Asiedu, Clement
Foulds, Kathryn E.
Roederer, Mario
Moliva, Juan I.
Sullivan, Nancy J.
author_facet Marcus, Hadar
Thompson, Emily
Zhou, Yan
Bailey, Michael
Donaldson, Mitzi M.
Stanley, Daphne A.
Asiedu, Clement
Foulds, Kathryn E.
Roederer, Mario
Moliva, Juan I.
Sullivan, Nancy J.
author_sort Marcus, Hadar
collection PubMed
description Heterologous prime-boost immunization regimens are a common strategy for many vaccines. DNA prime rAd5-GP boost immunization has been demonstrated to protect non-human primates against a lethal challenge of Ebola virus, a pathogen that causes fatal hemorrhagic disease in humans. This protection correlates with antibody responses and is also associated with IFNγ(+) TNFα(+) double positive CD8(+) T-cells. In this study, we compared single DNA vs. multiple DNA prime immunizations, and short vs. long time intervals between the DNA prime and the rAd5 boost to evaluate the impact of these different prime-boost strategies on vaccine-induced humoral and cellular responses in non-human primates. We demonstrated that DNA/rAd5 prime-boost strategies can be tailored to induce either CD4(+) T-cell or CD8(+) T-cell dominant responses while maintaining a high magnitude antibody response. Additionally, a single DNA prime immunization generated a stable memory response that could be boosted by rAd5 3 years later. These results suggest DNA/rAd5 prime-boost provides a flexible platform that can be fine-tuned to generate desirable T-cell memory responses.
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spelling pubmed-80063252021-03-30 Ebola-GP DNA Prime rAd5-GP Boost: Influence of Prime Frequency and Prime/Boost Time Interval on the Immune Response in Non-human Primates Marcus, Hadar Thompson, Emily Zhou, Yan Bailey, Michael Donaldson, Mitzi M. Stanley, Daphne A. Asiedu, Clement Foulds, Kathryn E. Roederer, Mario Moliva, Juan I. Sullivan, Nancy J. Front Immunol Immunology Heterologous prime-boost immunization regimens are a common strategy for many vaccines. DNA prime rAd5-GP boost immunization has been demonstrated to protect non-human primates against a lethal challenge of Ebola virus, a pathogen that causes fatal hemorrhagic disease in humans. This protection correlates with antibody responses and is also associated with IFNγ(+) TNFα(+) double positive CD8(+) T-cells. In this study, we compared single DNA vs. multiple DNA prime immunizations, and short vs. long time intervals between the DNA prime and the rAd5 boost to evaluate the impact of these different prime-boost strategies on vaccine-induced humoral and cellular responses in non-human primates. We demonstrated that DNA/rAd5 prime-boost strategies can be tailored to induce either CD4(+) T-cell or CD8(+) T-cell dominant responses while maintaining a high magnitude antibody response. Additionally, a single DNA prime immunization generated a stable memory response that could be boosted by rAd5 3 years later. These results suggest DNA/rAd5 prime-boost provides a flexible platform that can be fine-tuned to generate desirable T-cell memory responses. Frontiers Media S.A. 2021-03-09 /pmc/articles/PMC8006325/ /pubmed/33790899 http://dx.doi.org/10.3389/fimmu.2021.627688 Text en Copyright © 2021 Marcus, Thompson, Zhou, Bailey, Donaldson, Stanley, Asiedu, Foulds, Roederer, Moliva and Sullivan. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Marcus, Hadar
Thompson, Emily
Zhou, Yan
Bailey, Michael
Donaldson, Mitzi M.
Stanley, Daphne A.
Asiedu, Clement
Foulds, Kathryn E.
Roederer, Mario
Moliva, Juan I.
Sullivan, Nancy J.
Ebola-GP DNA Prime rAd5-GP Boost: Influence of Prime Frequency and Prime/Boost Time Interval on the Immune Response in Non-human Primates
title Ebola-GP DNA Prime rAd5-GP Boost: Influence of Prime Frequency and Prime/Boost Time Interval on the Immune Response in Non-human Primates
title_full Ebola-GP DNA Prime rAd5-GP Boost: Influence of Prime Frequency and Prime/Boost Time Interval on the Immune Response in Non-human Primates
title_fullStr Ebola-GP DNA Prime rAd5-GP Boost: Influence of Prime Frequency and Prime/Boost Time Interval on the Immune Response in Non-human Primates
title_full_unstemmed Ebola-GP DNA Prime rAd5-GP Boost: Influence of Prime Frequency and Prime/Boost Time Interval on the Immune Response in Non-human Primates
title_short Ebola-GP DNA Prime rAd5-GP Boost: Influence of Prime Frequency and Prime/Boost Time Interval on the Immune Response in Non-human Primates
title_sort ebola-gp dna prime rad5-gp boost: influence of prime frequency and prime/boost time interval on the immune response in non-human primates
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006325/
https://www.ncbi.nlm.nih.gov/pubmed/33790899
http://dx.doi.org/10.3389/fimmu.2021.627688
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