Biodistribution of the saponin-based adjuvant Matrix-M™ following intramuscular injection in mice
Novel adjuvants are extensively utilized in the development of safe and effective vaccines against emerging pathogens. Matrix-M™ adjuvant is a saponin-based adjuvant used in several active clinical development programs and in widespread use in the COVID-19 vaccine NVX-CoV2373. Here, we conducted a b...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-11-01
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| Series: | Frontiers in Drug Delivery |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fddev.2023.1279710/full |
| _version_ | 1827161250968109056 |
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| author | Cecilia Carnrot Berit Carow Anna-Karin E. Palm Eray Akpinar Per-Henrik Helgesson Ingrid Lekberg Osterman Emelie Bringeland Bryant Foreman Nita Patel Johan Bankefors Louis Fries Linda Stertman |
| author_facet | Cecilia Carnrot Berit Carow Anna-Karin E. Palm Eray Akpinar Per-Henrik Helgesson Ingrid Lekberg Osterman Emelie Bringeland Bryant Foreman Nita Patel Johan Bankefors Louis Fries Linda Stertman |
| author_sort | Cecilia Carnrot |
| collection | DOAJ |
| description | Novel adjuvants are extensively utilized in the development of safe and effective vaccines against emerging pathogens. Matrix-M™ adjuvant is a saponin-based adjuvant used in several active clinical development programs and in widespread use in the COVID-19 vaccine NVX-CoV2373. Here, we conducted a biodistribution study to better understand the mechanism of action and safety profile for Matrix-M™ adjuvant. Radiolabeled saponins or cholesterol were incorporated into Matrix-A™ particles, which represent 85% of Matrix-M™. Labeled Matrix-M™ adjuvant was given to mice by intramuscular injection with or without SARS-CoV-2 Spike protein. Radioactivity of the adjuvant components was quantified in local and systemic tissues at seven timepoints over a period of 1–168 h. The highest saponin levels were found at the 1-h timepoint at the injection site, in the draining (iliac) lymph nodes, and in urine. Saponins were rapidly cleared from these tissues, reaching very low levels by 48–72 h. Systemically, saponins were found at low levels in the plasma, kidneys, liver, and bone marrow, and were barely detectable in other investigated tissues. Cholesterol was also found at high levels at the injection site and in the draining lymph nodes. These levels declined rapidly at first, then plateaued at 24–48 h. Radiolabeled cholesterol was found at very low levels in other tissues at the earliest timepoints, until increasing and stabilizing after the 24-h timepoint, indicating entry into the endogenous cholesterol recycling pool. This study demonstrates a rapid distribution of Matrix-M™ adjuvant from the injection site to the draining lymph nodes, thus excluding a depot effect as central to the mechanism of action for this adjuvant. The diverging clearance patterns for saponins and cholesterol are suggestive of at least partial disassembly of the Matrix-particles, which has implications for the downstream effects of Matrix-M™ adjuvant on adaptive immune responses. Systemic exposure to toxicologically relevant tissues is very low. |
| first_indexed | 2024-03-11T10:31:32Z |
| format | Article |
| id | doaj.art-4481fd86955545dfac2655cb03706e44 |
| institution | Directory Open Access Journal |
| issn | 2674-0850 |
| language | English |
| last_indexed | 2025-03-21T00:25:56Z |
| publishDate | 2023-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Drug Delivery |
| spelling | doaj.art-4481fd86955545dfac2655cb03706e442024-08-03T07:15:50ZengFrontiers Media S.A.Frontiers in Drug Delivery2674-08502023-11-01310.3389/fddev.2023.12797101279710Biodistribution of the saponin-based adjuvant Matrix-M™ following intramuscular injection in miceCecilia Carnrot0Berit Carow1Anna-Karin E. Palm2Eray Akpinar3Per-Henrik Helgesson4Ingrid Lekberg Osterman5Emelie Bringeland6Bryant Foreman7Nita Patel8Johan Bankefors9Louis Fries10Linda Stertman11Adjuvant Immunology, Product Development, Novavax AB, Uppsala, SwedenAdjuvant Immunology, Product Development, Novavax AB, Uppsala, SwedenAdjuvant Immunology, Product Development, Novavax AB, Uppsala, SwedenAdjuvant Characterization, Product Development, Novavax AB, Uppsala, SwedenProduct Design and Formulation, Product Development, Novavax AB, Uppsala, SwedenAdjuvant Immunology, Product Development, Novavax AB, Uppsala, SwedenAdjuvant Immunology, Product Development, Novavax AB, Uppsala, SwedenVaccine Immunology, Novavax Inc., Gaithersburg, MD, United StatesVaccine Immunology, Novavax Inc., Gaithersburg, MD, United StatesAdjuvant Characterization, Product Development, Novavax AB, Uppsala, SwedenResearch and Development, Novavax Inc., Gaithersburg, MD, United StatesAdjuvant Immunology, Product Development, Novavax AB, Uppsala, SwedenNovel adjuvants are extensively utilized in the development of safe and effective vaccines against emerging pathogens. Matrix-M™ adjuvant is a saponin-based adjuvant used in several active clinical development programs and in widespread use in the COVID-19 vaccine NVX-CoV2373. Here, we conducted a biodistribution study to better understand the mechanism of action and safety profile for Matrix-M™ adjuvant. Radiolabeled saponins or cholesterol were incorporated into Matrix-A™ particles, which represent 85% of Matrix-M™. Labeled Matrix-M™ adjuvant was given to mice by intramuscular injection with or without SARS-CoV-2 Spike protein. Radioactivity of the adjuvant components was quantified in local and systemic tissues at seven timepoints over a period of 1–168 h. The highest saponin levels were found at the 1-h timepoint at the injection site, in the draining (iliac) lymph nodes, and in urine. Saponins were rapidly cleared from these tissues, reaching very low levels by 48–72 h. Systemically, saponins were found at low levels in the plasma, kidneys, liver, and bone marrow, and were barely detectable in other investigated tissues. Cholesterol was also found at high levels at the injection site and in the draining lymph nodes. These levels declined rapidly at first, then plateaued at 24–48 h. Radiolabeled cholesterol was found at very low levels in other tissues at the earliest timepoints, until increasing and stabilizing after the 24-h timepoint, indicating entry into the endogenous cholesterol recycling pool. This study demonstrates a rapid distribution of Matrix-M™ adjuvant from the injection site to the draining lymph nodes, thus excluding a depot effect as central to the mechanism of action for this adjuvant. The diverging clearance patterns for saponins and cholesterol are suggestive of at least partial disassembly of the Matrix-particles, which has implications for the downstream effects of Matrix-M™ adjuvant on adaptive immune responses. Systemic exposure to toxicologically relevant tissues is very low.https://www.frontiersin.org/articles/10.3389/fddev.2023.1279710/fullvaccineNVX-CoV2373draining lymph nodevaccine safetyCOVID-19mechanism of action |
| spellingShingle | Cecilia Carnrot Berit Carow Anna-Karin E. Palm Eray Akpinar Per-Henrik Helgesson Ingrid Lekberg Osterman Emelie Bringeland Bryant Foreman Nita Patel Johan Bankefors Louis Fries Linda Stertman Biodistribution of the saponin-based adjuvant Matrix-M™ following intramuscular injection in mice Frontiers in Drug Delivery vaccine NVX-CoV2373 draining lymph node vaccine safety COVID-19 mechanism of action |
| title | Biodistribution of the saponin-based adjuvant Matrix-M™ following intramuscular injection in mice |
| title_full | Biodistribution of the saponin-based adjuvant Matrix-M™ following intramuscular injection in mice |
| title_fullStr | Biodistribution of the saponin-based adjuvant Matrix-M™ following intramuscular injection in mice |
| title_full_unstemmed | Biodistribution of the saponin-based adjuvant Matrix-M™ following intramuscular injection in mice |
| title_short | Biodistribution of the saponin-based adjuvant Matrix-M™ following intramuscular injection in mice |
| title_sort | biodistribution of the saponin based adjuvant matrix m™ following intramuscular injection in mice |
| topic | vaccine NVX-CoV2373 draining lymph node vaccine safety COVID-19 mechanism of action |
| url | https://www.frontiersin.org/articles/10.3389/fddev.2023.1279710/full |
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