MINCLE and TLR9 agonists synergize to induce Th1/Th17 vaccine memory and mucosal recall in mice and non-human primates
Abstract Development of new vaccines tailored for difficult-to-target diseases is hampered by a lack of diverse adjuvants for human use, and none of the currently available adjuvants induce Th17 cells. Here, we develop a liposomal adjuvant, CAF®10b, that incorporates Mincle and Toll-like receptor 9...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-10-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-52863-9 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850181941562703872 |
|---|---|
| author | Joshua S. Woodworth Vanessa Contreras Dennis Christensen Thibaut Naninck Nidhal Kahlaoui Anne-Sophie Gallouët Sébastien Langlois Emma Burban Candie Joly Wesley Gros Nathalie Dereuddre-Bosquet Julie Morin Ming Liu Olsen Ida Rosenkrands Ann-Kathrin Stein Grith Krøyer Wood Frank Follmann Thomas Lindenstrøm Tu Hu Roger Le Grand Gabriel Kristian Pedersen Rasmus Mortensen |
| author_facet | Joshua S. Woodworth Vanessa Contreras Dennis Christensen Thibaut Naninck Nidhal Kahlaoui Anne-Sophie Gallouët Sébastien Langlois Emma Burban Candie Joly Wesley Gros Nathalie Dereuddre-Bosquet Julie Morin Ming Liu Olsen Ida Rosenkrands Ann-Kathrin Stein Grith Krøyer Wood Frank Follmann Thomas Lindenstrøm Tu Hu Roger Le Grand Gabriel Kristian Pedersen Rasmus Mortensen |
| author_sort | Joshua S. Woodworth |
| collection | DOAJ |
| description | Abstract Development of new vaccines tailored for difficult-to-target diseases is hampered by a lack of diverse adjuvants for human use, and none of the currently available adjuvants induce Th17 cells. Here, we develop a liposomal adjuvant, CAF®10b, that incorporates Mincle and Toll-like receptor 9 agonists. In parallel mouse and non-human primate studies comparing to CAF® adjuvants already in clinical trials, we report species-specific effects of adjuvant composition on the quality and magnitude of the responses. When combined with antigen, CAF®10b induces Th1 and Th17 responses and protection against a pulmonary infection with Mycobacterium tuberculosis in mice. In non-human primates, CAF®10b induces higher Th1 responses and robust Th17 responses detectable after six months, and systemic and pulmonary Th1 and Th17 recall responses, in a sterile model of local recall. Overall, CAF®10b drives robust memory antibody, Th1 and Th17 vaccine-responses via a non-mucosal immunization route across both rodent and primate species. |
| format | Article |
| id | doaj-art-247707a325064a6ea6e1237d4d196721 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-247707a325064a6ea6e1237d4d1967212025-08-20T02:17:47ZengNature PortfolioNature Communications2041-17232024-10-0115111610.1038/s41467-024-52863-9MINCLE and TLR9 agonists synergize to induce Th1/Th17 vaccine memory and mucosal recall in mice and non-human primatesJoshua S. Woodworth0Vanessa Contreras1Dennis Christensen2Thibaut Naninck3Nidhal Kahlaoui4Anne-Sophie Gallouët5Sébastien Langlois6Emma Burban7Candie Joly8Wesley Gros9Nathalie Dereuddre-Bosquet10Julie Morin11Ming Liu Olsen12Ida Rosenkrands13Ann-Kathrin Stein14Grith Krøyer Wood15Frank Follmann16Thomas Lindenstrøm17Tu Hu18Roger Le Grand19Gabriel Kristian Pedersen20Rasmus Mortensen21Department of Infectious Disease Immunology, Statens Serum InstitutUniversité Paris-Saclay, Inserm, CEA, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB/IDMIT/UMR1184)Department of Infectious Disease Immunology, Statens Serum InstitutUniversité Paris-Saclay, Inserm, CEA, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB/IDMIT/UMR1184)Université Paris-Saclay, Inserm, CEA, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB/IDMIT/UMR1184)Université Paris-Saclay, Inserm, CEA, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB/IDMIT/UMR1184)Université Paris-Saclay, Inserm, CEA, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB/IDMIT/UMR1184)Université Paris-Saclay, Inserm, CEA, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB/IDMIT/UMR1184)Université Paris-Saclay, Inserm, CEA, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB/IDMIT/UMR1184)Université Paris-Saclay, Inserm, CEA, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB/IDMIT/UMR1184)Université Paris-Saclay, Inserm, CEA, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB/IDMIT/UMR1184)Université Paris-Saclay, Inserm, CEA, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB/IDMIT/UMR1184)Department of Infectious Disease Immunology, Statens Serum InstitutDepartment of Infectious Disease Immunology, Statens Serum InstitutDepartment of Vaccine Development, Statens Serum InstitutDepartment of Vaccine Development, Statens Serum InstitutDepartment of Infectious Disease Immunology, Statens Serum InstitutDepartment of Infectious Disease Immunology, Statens Serum InstitutDepartment of Infectious Disease Immunology, Statens Serum InstitutUniversité Paris-Saclay, Inserm, CEA, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB/IDMIT/UMR1184)Department of Infectious Disease Immunology, Statens Serum InstitutDepartment of Infectious Disease Immunology, Statens Serum InstitutAbstract Development of new vaccines tailored for difficult-to-target diseases is hampered by a lack of diverse adjuvants for human use, and none of the currently available adjuvants induce Th17 cells. Here, we develop a liposomal adjuvant, CAF®10b, that incorporates Mincle and Toll-like receptor 9 agonists. In parallel mouse and non-human primate studies comparing to CAF® adjuvants already in clinical trials, we report species-specific effects of adjuvant composition on the quality and magnitude of the responses. When combined with antigen, CAF®10b induces Th1 and Th17 responses and protection against a pulmonary infection with Mycobacterium tuberculosis in mice. In non-human primates, CAF®10b induces higher Th1 responses and robust Th17 responses detectable after six months, and systemic and pulmonary Th1 and Th17 recall responses, in a sterile model of local recall. Overall, CAF®10b drives robust memory antibody, Th1 and Th17 vaccine-responses via a non-mucosal immunization route across both rodent and primate species.https://doi.org/10.1038/s41467-024-52863-9 |
| spellingShingle | Joshua S. Woodworth Vanessa Contreras Dennis Christensen Thibaut Naninck Nidhal Kahlaoui Anne-Sophie Gallouët Sébastien Langlois Emma Burban Candie Joly Wesley Gros Nathalie Dereuddre-Bosquet Julie Morin Ming Liu Olsen Ida Rosenkrands Ann-Kathrin Stein Grith Krøyer Wood Frank Follmann Thomas Lindenstrøm Tu Hu Roger Le Grand Gabriel Kristian Pedersen Rasmus Mortensen MINCLE and TLR9 agonists synergize to induce Th1/Th17 vaccine memory and mucosal recall in mice and non-human primates Nature Communications |
| title | MINCLE and TLR9 agonists synergize to induce Th1/Th17 vaccine memory and mucosal recall in mice and non-human primates |
| title_full | MINCLE and TLR9 agonists synergize to induce Th1/Th17 vaccine memory and mucosal recall in mice and non-human primates |
| title_fullStr | MINCLE and TLR9 agonists synergize to induce Th1/Th17 vaccine memory and mucosal recall in mice and non-human primates |
| title_full_unstemmed | MINCLE and TLR9 agonists synergize to induce Th1/Th17 vaccine memory and mucosal recall in mice and non-human primates |
| title_short | MINCLE and TLR9 agonists synergize to induce Th1/Th17 vaccine memory and mucosal recall in mice and non-human primates |
| title_sort | mincle and tlr9 agonists synergize to induce th1 th17 vaccine memory and mucosal recall in mice and non human primates |
| url | https://doi.org/10.1038/s41467-024-52863-9 |
| work_keys_str_mv | AT joshuaswoodworth mincleandtlr9agonistssynergizetoinduceth1th17vaccinememoryandmucosalrecallinmiceandnonhumanprimates AT vanessacontreras mincleandtlr9agonistssynergizetoinduceth1th17vaccinememoryandmucosalrecallinmiceandnonhumanprimates AT dennischristensen mincleandtlr9agonistssynergizetoinduceth1th17vaccinememoryandmucosalrecallinmiceandnonhumanprimates AT thibautnaninck mincleandtlr9agonistssynergizetoinduceth1th17vaccinememoryandmucosalrecallinmiceandnonhumanprimates AT nidhalkahlaoui mincleandtlr9agonistssynergizetoinduceth1th17vaccinememoryandmucosalrecallinmiceandnonhumanprimates AT annesophiegallouet mincleandtlr9agonistssynergizetoinduceth1th17vaccinememoryandmucosalrecallinmiceandnonhumanprimates AT sebastienlanglois mincleandtlr9agonistssynergizetoinduceth1th17vaccinememoryandmucosalrecallinmiceandnonhumanprimates AT emmaburban mincleandtlr9agonistssynergizetoinduceth1th17vaccinememoryandmucosalrecallinmiceandnonhumanprimates AT candiejoly mincleandtlr9agonistssynergizetoinduceth1th17vaccinememoryandmucosalrecallinmiceandnonhumanprimates AT wesleygros mincleandtlr9agonistssynergizetoinduceth1th17vaccinememoryandmucosalrecallinmiceandnonhumanprimates AT nathaliedereuddrebosquet mincleandtlr9agonistssynergizetoinduceth1th17vaccinememoryandmucosalrecallinmiceandnonhumanprimates AT juliemorin mincleandtlr9agonistssynergizetoinduceth1th17vaccinememoryandmucosalrecallinmiceandnonhumanprimates AT mingliuolsen mincleandtlr9agonistssynergizetoinduceth1th17vaccinememoryandmucosalrecallinmiceandnonhumanprimates AT idarosenkrands mincleandtlr9agonistssynergizetoinduceth1th17vaccinememoryandmucosalrecallinmiceandnonhumanprimates AT annkathrinstein mincleandtlr9agonistssynergizetoinduceth1th17vaccinememoryandmucosalrecallinmiceandnonhumanprimates AT grithkrøyerwood mincleandtlr9agonistssynergizetoinduceth1th17vaccinememoryandmucosalrecallinmiceandnonhumanprimates AT frankfollmann mincleandtlr9agonistssynergizetoinduceth1th17vaccinememoryandmucosalrecallinmiceandnonhumanprimates AT thomaslindenstrøm mincleandtlr9agonistssynergizetoinduceth1th17vaccinememoryandmucosalrecallinmiceandnonhumanprimates AT tuhu mincleandtlr9agonistssynergizetoinduceth1th17vaccinememoryandmucosalrecallinmiceandnonhumanprimates AT rogerlegrand mincleandtlr9agonistssynergizetoinduceth1th17vaccinememoryandmucosalrecallinmiceandnonhumanprimates AT gabrielkristianpedersen mincleandtlr9agonistssynergizetoinduceth1th17vaccinememoryandmucosalrecallinmiceandnonhumanprimates AT rasmusmortensen mincleandtlr9agonistssynergizetoinduceth1th17vaccinememoryandmucosalrecallinmiceandnonhumanprimates |