Matrix-M adjuvant triggers inflammasome activation and enables antigen cross-presentation through induction of lysosomal membrane permeabilization
Abstract Matrix-M® adjuvant, containing saponins, delivers a potent adjuvant effect and good safety profile. Given that Matrix-M is composed of Matrix-A and Matrix-C particles, comprising different saponin fractions, understanding their distinct roles can provide deeper insight into the mechanism of...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-08-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-025-01243-5 |
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| author | Behdad Zarnegar Berit Carow Jens Eriksson Eva Spennare Pontus Öhlund Eray Akpinar Emelie Bringeland Ingrid Lekberg Osterman Lena Lundqvist Johanna Antti Niklas Handin Per-Henrik Helgesson Johan Bankefors Karin Lövgren Bengtsson Mikael E. Sellin Anna-Karin E. Palm Linda Stertman Carolina Lunderius Andersson |
| author_facet | Behdad Zarnegar Berit Carow Jens Eriksson Eva Spennare Pontus Öhlund Eray Akpinar Emelie Bringeland Ingrid Lekberg Osterman Lena Lundqvist Johanna Antti Niklas Handin Per-Henrik Helgesson Johan Bankefors Karin Lövgren Bengtsson Mikael E. Sellin Anna-Karin E. Palm Linda Stertman Carolina Lunderius Andersson |
| author_sort | Behdad Zarnegar |
| collection | DOAJ |
| description | Abstract Matrix-M® adjuvant, containing saponins, delivers a potent adjuvant effect and good safety profile. Given that Matrix-M is composed of Matrix-A and Matrix-C particles, comprising different saponin fractions, understanding their distinct roles can provide deeper insight into the mechanism of action of Matrix-M and guide future applications. Here, we demonstrate that the antigen and Matrix-M, Matrix-A, or Matrix-C colocalize in lysosomes following uptake by bone marrow–derived dendritic cells. Matrix-M, Matrix-A, and Matrix-C induce lysosomal membrane permeabilization (LMP), but Matrix-C shows the highest LMP potential. LMP is required for interleukin (IL)-1β and IL-18 secretion in vitro. In vivo, a robust adjuvant effect of Matrix-M, Matrix-A, and Matrix-C is observed, both in the presence and absence of the NLRP3 inflammasome. LMP induced by Matrix-M, as well as Matrix-A and Matrix-C, also enables antigen cross-presentation. Thus, Matrix-induced LMP explains the capability of Matrix-M–adjuvanted protein vaccines to induce CD8+ T-cell responses. |
| format | Article |
| id | doaj-art-c282f0c5930842268f5195d36fb2de30 |
| institution | Kabale University |
| issn | 2059-0105 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj-art-c282f0c5930842268f5195d36fb2de302025-08-20T03:42:19ZengNature Portfolionpj Vaccines2059-01052025-08-0110111810.1038/s41541-025-01243-5Matrix-M adjuvant triggers inflammasome activation and enables antigen cross-presentation through induction of lysosomal membrane permeabilizationBehdad Zarnegar0Berit Carow1Jens Eriksson2Eva Spennare3Pontus Öhlund4Eray Akpinar5Emelie Bringeland6Ingrid Lekberg Osterman7Lena Lundqvist8Johanna Antti9Niklas Handin10Per-Henrik Helgesson11Johan Bankefors12Karin Lövgren Bengtsson13Mikael E. Sellin14Anna-Karin E. Palm15Linda Stertman16Carolina Lunderius Andersson17Novavax ABNovavax ABDepartment of Medical Biochemistry and Microbiology, Uppsala UniversityNovavax ABNovavax ABNovavax ABNovavax ABNovavax ABNovavax ABNovavax ABNovavax ABNovavax ABNovavax ABNovavax ABDepartment of Medical Biochemistry and Microbiology, Uppsala UniversityNovavax ABNovavax ABNovavax ABAbstract Matrix-M® adjuvant, containing saponins, delivers a potent adjuvant effect and good safety profile. Given that Matrix-M is composed of Matrix-A and Matrix-C particles, comprising different saponin fractions, understanding their distinct roles can provide deeper insight into the mechanism of action of Matrix-M and guide future applications. Here, we demonstrate that the antigen and Matrix-M, Matrix-A, or Matrix-C colocalize in lysosomes following uptake by bone marrow–derived dendritic cells. Matrix-M, Matrix-A, and Matrix-C induce lysosomal membrane permeabilization (LMP), but Matrix-C shows the highest LMP potential. LMP is required for interleukin (IL)-1β and IL-18 secretion in vitro. In vivo, a robust adjuvant effect of Matrix-M, Matrix-A, and Matrix-C is observed, both in the presence and absence of the NLRP3 inflammasome. LMP induced by Matrix-M, as well as Matrix-A and Matrix-C, also enables antigen cross-presentation. Thus, Matrix-induced LMP explains the capability of Matrix-M–adjuvanted protein vaccines to induce CD8+ T-cell responses.https://doi.org/10.1038/s41541-025-01243-5 |
| spellingShingle | Behdad Zarnegar Berit Carow Jens Eriksson Eva Spennare Pontus Öhlund Eray Akpinar Emelie Bringeland Ingrid Lekberg Osterman Lena Lundqvist Johanna Antti Niklas Handin Per-Henrik Helgesson Johan Bankefors Karin Lövgren Bengtsson Mikael E. Sellin Anna-Karin E. Palm Linda Stertman Carolina Lunderius Andersson Matrix-M adjuvant triggers inflammasome activation and enables antigen cross-presentation through induction of lysosomal membrane permeabilization npj Vaccines |
| title | Matrix-M adjuvant triggers inflammasome activation and enables antigen cross-presentation through induction of lysosomal membrane permeabilization |
| title_full | Matrix-M adjuvant triggers inflammasome activation and enables antigen cross-presentation through induction of lysosomal membrane permeabilization |
| title_fullStr | Matrix-M adjuvant triggers inflammasome activation and enables antigen cross-presentation through induction of lysosomal membrane permeabilization |
| title_full_unstemmed | Matrix-M adjuvant triggers inflammasome activation and enables antigen cross-presentation through induction of lysosomal membrane permeabilization |
| title_short | Matrix-M adjuvant triggers inflammasome activation and enables antigen cross-presentation through induction of lysosomal membrane permeabilization |
| title_sort | matrix m adjuvant triggers inflammasome activation and enables antigen cross presentation through induction of lysosomal membrane permeabilization |
| url | https://doi.org/10.1038/s41541-025-01243-5 |
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