Highly immunogenic DNA/LION nanocarrier vaccine potently activates lymph nodes inducing long-lasting immunity in macaques

Summary: A SARS-CoV-2 spike DNA vaccine formulated with a cationic nanoparticle emulsion (LION) was tested in Rhesus macaques. It induced robust, long-lasting (>2 years) cellular and humoral immunity, including increased neutralization breadth. T cell responses were predominantly CD8+, in contras...

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Main Authors: Sevasti Karaliota, Maha Moussa, Margherita Rosati, Santhi Devasundaram, Soumya Sengupta, Katherine C. Goldfarbmuren, Robert Burns, Jenifer Bear, Dimitris Stellas, Elizabeth A. Urban, Claire Deleage, Amit P. Khandhar, Jesse Erasmus, Peter Berglund, Steven G. Reed, George N. Pavlakis, Barbara K. Felber
Format: Article
Language:English
Published: Elsevier 2025-04-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004225004936
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author Sevasti Karaliota
Maha Moussa
Margherita Rosati
Santhi Devasundaram
Soumya Sengupta
Katherine C. Goldfarbmuren
Robert Burns
Jenifer Bear
Dimitris Stellas
Elizabeth A. Urban
Claire Deleage
Amit P. Khandhar
Jesse Erasmus
Peter Berglund
Steven G. Reed
George N. Pavlakis
Barbara K. Felber
author_facet Sevasti Karaliota
Maha Moussa
Margherita Rosati
Santhi Devasundaram
Soumya Sengupta
Katherine C. Goldfarbmuren
Robert Burns
Jenifer Bear
Dimitris Stellas
Elizabeth A. Urban
Claire Deleage
Amit P. Khandhar
Jesse Erasmus
Peter Berglund
Steven G. Reed
George N. Pavlakis
Barbara K. Felber
author_sort Sevasti Karaliota
collection DOAJ
description Summary: A SARS-CoV-2 spike DNA vaccine formulated with a cationic nanoparticle emulsion (LION) was tested in Rhesus macaques. It induced robust, long-lasting (>2 years) cellular and humoral immunity, including increased neutralization breadth. T cell responses were predominantly CD8+, in contrast to other DNA vaccines. A rapid transient cytokine/chemokine response was associated with expansion and trafficking of myeloid cells and lymphocytes. Increased proliferation and dynamic changes between blood and lymph node (LN) were found for monocyte-derived cells, dendritic cells, and B and T cells, resulting in activation of LN and expansion of germinal centers (GCs), likely critical in shaping long-lasting adaptive immunity. Significant GC expansion of B, CD4−, and CD8− cells, including the Tfc3 subset, reflects a balanced immune response, including antibody (Ab) development. DNA/LION vaccination activates myeloid and lymphoid cells in blood and LN and promotes effective antigen presentation, resulting in sustained antigen-specific cellular and humoral responses, emerging as an effective DNA vaccine delivery platform.
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issn 2589-0042
language English
publishDate 2025-04-01
publisher Elsevier
record_format Article
series iScience
spelling doaj-art-eaebaf88db0e45e8b06d10e9c352147f2025-08-20T02:10:20ZengElsevieriScience2589-00422025-04-0128411223210.1016/j.isci.2025.112232Highly immunogenic DNA/LION nanocarrier vaccine potently activates lymph nodes inducing long-lasting immunity in macaquesSevasti Karaliota0Maha Moussa1Margherita Rosati2Santhi Devasundaram3Soumya Sengupta4Katherine C. Goldfarbmuren5Robert Burns6Jenifer Bear7Dimitris Stellas8Elizabeth A. Urban9Claire Deleage10Amit P. Khandhar11Jesse Erasmus12Peter Berglund13Steven G. Reed14George N. Pavlakis15Barbara K. Felber16Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA; Basic Science Program, Leidos Biomedical Research, Inc., Frederick, MD, USAHuman Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, MD, USAHuman Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, MD, USAHuman Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, MD, USAHuman Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, MD, USAAdvanced Biomedical Computational Science, Leidos Biomedical Research, Inc., Frederick, MD, USA; Vaccine Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USAHuman Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, MD, USAHuman Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, MD, USAHuman Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, MD, USAAIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USAAIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USAHDT Bio Corp, Seattle, WA, USAHDT Bio Corp, Seattle, WA, USAHDT Bio Corp, Seattle, WA, USAHDT Bio Corp, Seattle, WA, USACenter for Cancer Research, National Cancer Institute, Frederick, MD, USAHuman Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA; Corresponding authorSummary: A SARS-CoV-2 spike DNA vaccine formulated with a cationic nanoparticle emulsion (LION) was tested in Rhesus macaques. It induced robust, long-lasting (>2 years) cellular and humoral immunity, including increased neutralization breadth. T cell responses were predominantly CD8+, in contrast to other DNA vaccines. A rapid transient cytokine/chemokine response was associated with expansion and trafficking of myeloid cells and lymphocytes. Increased proliferation and dynamic changes between blood and lymph node (LN) were found for monocyte-derived cells, dendritic cells, and B and T cells, resulting in activation of LN and expansion of germinal centers (GCs), likely critical in shaping long-lasting adaptive immunity. Significant GC expansion of B, CD4−, and CD8− cells, including the Tfc3 subset, reflects a balanced immune response, including antibody (Ab) development. DNA/LION vaccination activates myeloid and lymphoid cells in blood and LN and promotes effective antigen presentation, resulting in sustained antigen-specific cellular and humoral responses, emerging as an effective DNA vaccine delivery platform.http://www.sciencedirect.com/science/article/pii/S2589004225004936Natural sciencesBiological sciencesImmunologyImmune responseBiotechnologyNanotechnology
spellingShingle Sevasti Karaliota
Maha Moussa
Margherita Rosati
Santhi Devasundaram
Soumya Sengupta
Katherine C. Goldfarbmuren
Robert Burns
Jenifer Bear
Dimitris Stellas
Elizabeth A. Urban
Claire Deleage
Amit P. Khandhar
Jesse Erasmus
Peter Berglund
Steven G. Reed
George N. Pavlakis
Barbara K. Felber
Highly immunogenic DNA/LION nanocarrier vaccine potently activates lymph nodes inducing long-lasting immunity in macaques
iScience
Natural sciences
Biological sciences
Immunology
Immune response
Biotechnology
Nanotechnology
title Highly immunogenic DNA/LION nanocarrier vaccine potently activates lymph nodes inducing long-lasting immunity in macaques
title_full Highly immunogenic DNA/LION nanocarrier vaccine potently activates lymph nodes inducing long-lasting immunity in macaques
title_fullStr Highly immunogenic DNA/LION nanocarrier vaccine potently activates lymph nodes inducing long-lasting immunity in macaques
title_full_unstemmed Highly immunogenic DNA/LION nanocarrier vaccine potently activates lymph nodes inducing long-lasting immunity in macaques
title_short Highly immunogenic DNA/LION nanocarrier vaccine potently activates lymph nodes inducing long-lasting immunity in macaques
title_sort highly immunogenic dna lion nanocarrier vaccine potently activates lymph nodes inducing long lasting immunity in macaques
topic Natural sciences
Biological sciences
Immunology
Immune response
Biotechnology
Nanotechnology
url http://www.sciencedirect.com/science/article/pii/S2589004225004936
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