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A novel adjuvant formulation induces robust Th1/Th17 memory and mucosal recall responses in Non-Human Primates
After clean drinking water, vaccination is the most impactful global health intervention. However, development of new vaccines against difficult-to-target diseases is hampered by the lack of diverse adjuvants for human use. Of particular interest, none of the currently available adjuvants induce Th1...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9980079/ https://www.ncbi.nlm.nih.gov/pubmed/36865310 http://dx.doi.org/10.1101/2023.02.23.529651 |
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author | Woodworth, Joshua S Contreras, Vanessa Christensen, Dennis Naninck, Thibaut Kahlaoui, Nidhal Gallouët, Anne-Sophie Langlois, Sébastien Burban, Emma Joly, Candie Gros, Wesley Dereuddre-Bosquet, Nathalie Morin, Julie Olsen, Ming Liu Rosenkrands, Ida Stein, Ann-Kathrin Wood, Grith Krøyer Follmann, Frank Lindenstrøm, Thomas LeGrand, Roger Pedersen, Gabriel Kristian Mortensen, Rasmus |
author_facet | Woodworth, Joshua S Contreras, Vanessa Christensen, Dennis Naninck, Thibaut Kahlaoui, Nidhal Gallouët, Anne-Sophie Langlois, Sébastien Burban, Emma Joly, Candie Gros, Wesley Dereuddre-Bosquet, Nathalie Morin, Julie Olsen, Ming Liu Rosenkrands, Ida Stein, Ann-Kathrin Wood, Grith Krøyer Follmann, Frank Lindenstrøm, Thomas LeGrand, Roger Pedersen, Gabriel Kristian Mortensen, Rasmus |
author_sort | Woodworth, Joshua S |
collection | PubMed |
description | After clean drinking water, vaccination is the most impactful global health intervention. However, development of new vaccines against difficult-to-target diseases is hampered by the lack of diverse adjuvants for human use. Of particular interest, none of the currently available adjuvants induce Th17 cells. Here, we develop and test an improved liposomal adjuvant, termed CAF(®)10b, that incorporates a TLR-9 agonist. In a head-to-head study in non-human primates (NHPs), immunization with antigen adjuvanted with CAF(®)10b induced significantly increased antibody and cellular immune responses compared to previous CAF(®) adjuvants, already in clinical trials. This was not seen in the mouse model, demonstrating that adjuvant effects can be highly species specific. Importantly, intramuscular immunization of NHPs with CAF(®)10b induced robust Th17 responses that were observed in circulation half a year after vaccination. Furthermore, subsequent instillation of unadjuvanted antigen into the skin and lungs of these memory animals led to significant recall responses including transient local lung inflammation observed by Positron Emission Tomography-Computed Tomography (PET-CT), elevated antibody titers, and expanded systemic and local Th1 and Th17 responses, including >20% antigen-specific T cells in the bronchoalveolar lavage. Overall, CAF(®)10b demonstrated an adjuvant able to drive true memory antibody, Th1 and Th17 vaccine-responses across rodent and primate species, supporting its translational potential. |
format | Online Article Text |
id | pubmed-9980079 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-99800792023-03-03 A novel adjuvant formulation induces robust Th1/Th17 memory and mucosal recall responses in Non-Human Primates Woodworth, Joshua S Contreras, Vanessa Christensen, Dennis Naninck, Thibaut Kahlaoui, Nidhal Gallouët, Anne-Sophie Langlois, Sébastien Burban, Emma Joly, Candie Gros, Wesley Dereuddre-Bosquet, Nathalie Morin, Julie Olsen, Ming Liu Rosenkrands, Ida Stein, Ann-Kathrin Wood, Grith Krøyer Follmann, Frank Lindenstrøm, Thomas LeGrand, Roger Pedersen, Gabriel Kristian Mortensen, Rasmus bioRxiv Article After clean drinking water, vaccination is the most impactful global health intervention. However, development of new vaccines against difficult-to-target diseases is hampered by the lack of diverse adjuvants for human use. Of particular interest, none of the currently available adjuvants induce Th17 cells. Here, we develop and test an improved liposomal adjuvant, termed CAF(®)10b, that incorporates a TLR-9 agonist. In a head-to-head study in non-human primates (NHPs), immunization with antigen adjuvanted with CAF(®)10b induced significantly increased antibody and cellular immune responses compared to previous CAF(®) adjuvants, already in clinical trials. This was not seen in the mouse model, demonstrating that adjuvant effects can be highly species specific. Importantly, intramuscular immunization of NHPs with CAF(®)10b induced robust Th17 responses that were observed in circulation half a year after vaccination. Furthermore, subsequent instillation of unadjuvanted antigen into the skin and lungs of these memory animals led to significant recall responses including transient local lung inflammation observed by Positron Emission Tomography-Computed Tomography (PET-CT), elevated antibody titers, and expanded systemic and local Th1 and Th17 responses, including >20% antigen-specific T cells in the bronchoalveolar lavage. Overall, CAF(®)10b demonstrated an adjuvant able to drive true memory antibody, Th1 and Th17 vaccine-responses across rodent and primate species, supporting its translational potential. Cold Spring Harbor Laboratory 2023-02-23 /pmc/articles/PMC9980079/ /pubmed/36865310 http://dx.doi.org/10.1101/2023.02.23.529651 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Article Woodworth, Joshua S Contreras, Vanessa Christensen, Dennis Naninck, Thibaut Kahlaoui, Nidhal Gallouët, Anne-Sophie Langlois, Sébastien Burban, Emma Joly, Candie Gros, Wesley Dereuddre-Bosquet, Nathalie Morin, Julie Olsen, Ming Liu Rosenkrands, Ida Stein, Ann-Kathrin Wood, Grith Krøyer Follmann, Frank Lindenstrøm, Thomas LeGrand, Roger Pedersen, Gabriel Kristian Mortensen, Rasmus A novel adjuvant formulation induces robust Th1/Th17 memory and mucosal recall responses in Non-Human Primates |
title | A novel adjuvant formulation induces robust Th1/Th17 memory and mucosal recall responses in Non-Human Primates |
title_full | A novel adjuvant formulation induces robust Th1/Th17 memory and mucosal recall responses in Non-Human Primates |
title_fullStr | A novel adjuvant formulation induces robust Th1/Th17 memory and mucosal recall responses in Non-Human Primates |
title_full_unstemmed | A novel adjuvant formulation induces robust Th1/Th17 memory and mucosal recall responses in Non-Human Primates |
title_short | A novel adjuvant formulation induces robust Th1/Th17 memory and mucosal recall responses in Non-Human Primates |
title_sort | novel adjuvant formulation induces robust th1/th17 memory and mucosal recall responses in non-human primates |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9980079/ https://www.ncbi.nlm.nih.gov/pubmed/36865310 http://dx.doi.org/10.1101/2023.02.23.529651 |
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