MRI/PET multimodal imaging of the innate immune response in skeletal muscle and draining lymph node post vaccination in rats
The goal of this study was to utilize a multimodal magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging approach to assess the local innate immune response in skeletal muscle and draining lymph node following vaccination in rats using two different vaccine platforms (AS01...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1081156/full |
| _version_ | 1797956009104244736 |
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| author | Saaussan Madi Fang Xie Kamyar Farhangi Chih-Yang Hsu Shih-Hsun Cheng Tolulope Aweda Bhasker Radaram Stephanie Slania Tammy Lambert Mary Rambo Tina Skedzielewski Austin Cole Valeriia Sherina Shannon McKearnan Hoang Tran Hasan Alsaid Minh Doan Alan H. Stokes Derek T. O’Hagan Giulietta Maruggi Sylvie Bertholet Stéphane T. Temmerman Russell Johnson Beat M. Jucker |
| author_facet | Saaussan Madi Fang Xie Kamyar Farhangi Chih-Yang Hsu Shih-Hsun Cheng Tolulope Aweda Bhasker Radaram Stephanie Slania Tammy Lambert Mary Rambo Tina Skedzielewski Austin Cole Valeriia Sherina Shannon McKearnan Hoang Tran Hasan Alsaid Minh Doan Alan H. Stokes Derek T. O’Hagan Giulietta Maruggi Sylvie Bertholet Stéphane T. Temmerman Russell Johnson Beat M. Jucker |
| author_sort | Saaussan Madi |
| collection | DOAJ |
| description | The goal of this study was to utilize a multimodal magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging approach to assess the local innate immune response in skeletal muscle and draining lymph node following vaccination in rats using two different vaccine platforms (AS01 adjuvanted protein and lipid nanoparticle (LNP) encapsulated Self-Amplifying mRNA (SAM)). MRI and 18FDG PET imaging were performed temporally at baseline, 4, 24, 48, and 72 hr post Prime and Prime-Boost vaccination in hindlimb with Cytomegalovirus (CMV) gB and pentamer proteins formulated with AS01, LNP encapsulated CMV gB protein-encoding SAM (CMV SAM), AS01 or with LNP carrier controls. Both CMV AS01 and CMV SAM resulted in a rapid MRI and PET signal enhancement in hindlimb muscles and draining popliteal lymph node reflecting innate and possibly adaptive immune response. MRI signal enhancement and total 18FDG uptake observed in the hindlimb was greater in the CMV SAM vs CMV AS01 group (↑2.3 – 4.3-fold in AUC) and the MRI signal enhancement peak and duration were temporally shifted right in the CMV SAM group following both Prime and Prime-Boost administration. While cytokine profiles were similar among groups, there was good temporal correlation only between IL-6, IL-13, and MRI/PET endpoints. Imaging mass cytometry was performed on lymph node sections at 72 hr post Prime and Prime-Boost vaccination to characterize the innate and adaptive immune cell signatures. Cell proximity analysis indicated that each follicular dendritic cell interacted with more follicular B cells in the CMV AS01 than in the CMV SAM group, supporting the stronger humoral immune response observed in the CMV AS01 group. A strong correlation between lymph node MRI T2 value and nearest-neighbor analysis of follicular dendritic cell and follicular B cells was observed (r=0.808, P<0.01). These data suggest that spatiotemporal imaging data together with AI/ML approaches may help establish whether in vivo imaging biomarkers can predict local and systemic immune responses following vaccination. |
| first_indexed | 2024-04-10T23:42:06Z |
| format | Article |
| id | doaj.art-f8cb07fbb3844bfdbcb71445fb51ca9e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T23:42:06Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-f8cb07fbb3844bfdbcb71445fb51ca9e2023-01-11T06:44:45ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-01-011310.3389/fimmu.2022.10811561081156MRI/PET multimodal imaging of the innate immune response in skeletal muscle and draining lymph node post vaccination in ratsSaaussan Madi0Fang Xie1Kamyar Farhangi2Chih-Yang Hsu3Shih-Hsun Cheng4Tolulope Aweda5Bhasker Radaram6Stephanie Slania7Tammy Lambert8Mary Rambo9Tina Skedzielewski10Austin Cole11Valeriia Sherina12Shannon McKearnan13Hoang Tran14Hasan Alsaid15Minh Doan16Alan H. Stokes17Derek T. O’Hagan18Giulietta Maruggi19Sylvie Bertholet20Stéphane T. Temmerman21Russell Johnson22Beat M. Jucker23Bioimaging, GSK, Collegeville, PA, United StatesBioimaging, GSK, Collegeville, PA, United StatesBioimaging, GSK, Collegeville, PA, United StatesBioimaging, GSK, Collegeville, PA, United StatesBioimaging, GSK, Collegeville, PA, United StatesBioimaging, GSK, Collegeville, PA, United StatesBioimaging, GSK, Collegeville, PA, United StatesBioimaging, GSK, Collegeville, PA, United StatesNon Clinical Safety, GSK, Collegeville, PA, United StatesBioimaging, GSK, Collegeville, PA, United StatesBioimaging, GSK, Collegeville, PA, United StatesResearch Statistics, GSK, Collegeville, PA, United StatesResearch Statistics, GSK, Collegeville, PA, United StatesResearch Statistics, GSK, Collegeville, PA, United StatesResearch Statistics, GSK, Collegeville, PA, United StatesBioimaging, GSK, Collegeville, PA, United StatesBioimaging, GSK, Collegeville, PA, United StatesNon Clinical Safety, GSK, Collegeville, PA, United StatesVaccines Research & Development, GSK, Rockville, MD, United StatesVaccines Research & Development, GSK, Rockville, MD, United StatesVaccines Research & Development, GSK, Rockville, MD, United StatesVaccines Research & Development, GSK, Rixensart, BelgiumVaccines Research & Development, GSK, Rockville, MD, United StatesClinical Imaging, GSK, Collegeville, PA, United StatesThe goal of this study was to utilize a multimodal magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging approach to assess the local innate immune response in skeletal muscle and draining lymph node following vaccination in rats using two different vaccine platforms (AS01 adjuvanted protein and lipid nanoparticle (LNP) encapsulated Self-Amplifying mRNA (SAM)). MRI and 18FDG PET imaging were performed temporally at baseline, 4, 24, 48, and 72 hr post Prime and Prime-Boost vaccination in hindlimb with Cytomegalovirus (CMV) gB and pentamer proteins formulated with AS01, LNP encapsulated CMV gB protein-encoding SAM (CMV SAM), AS01 or with LNP carrier controls. Both CMV AS01 and CMV SAM resulted in a rapid MRI and PET signal enhancement in hindlimb muscles and draining popliteal lymph node reflecting innate and possibly adaptive immune response. MRI signal enhancement and total 18FDG uptake observed in the hindlimb was greater in the CMV SAM vs CMV AS01 group (↑2.3 – 4.3-fold in AUC) and the MRI signal enhancement peak and duration were temporally shifted right in the CMV SAM group following both Prime and Prime-Boost administration. While cytokine profiles were similar among groups, there was good temporal correlation only between IL-6, IL-13, and MRI/PET endpoints. Imaging mass cytometry was performed on lymph node sections at 72 hr post Prime and Prime-Boost vaccination to characterize the innate and adaptive immune cell signatures. Cell proximity analysis indicated that each follicular dendritic cell interacted with more follicular B cells in the CMV AS01 than in the CMV SAM group, supporting the stronger humoral immune response observed in the CMV AS01 group. A strong correlation between lymph node MRI T2 value and nearest-neighbor analysis of follicular dendritic cell and follicular B cells was observed (r=0.808, P<0.01). These data suggest that spatiotemporal imaging data together with AI/ML approaches may help establish whether in vivo imaging biomarkers can predict local and systemic immune responses following vaccination.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1081156/fullinnate immune activationmagnetic resonance imagingpositron emission tomographyself-amplifying mRNAlipid nanoparticleAS01 |
| spellingShingle | Saaussan Madi Fang Xie Kamyar Farhangi Chih-Yang Hsu Shih-Hsun Cheng Tolulope Aweda Bhasker Radaram Stephanie Slania Tammy Lambert Mary Rambo Tina Skedzielewski Austin Cole Valeriia Sherina Shannon McKearnan Hoang Tran Hasan Alsaid Minh Doan Alan H. Stokes Derek T. O’Hagan Giulietta Maruggi Sylvie Bertholet Stéphane T. Temmerman Russell Johnson Beat M. Jucker MRI/PET multimodal imaging of the innate immune response in skeletal muscle and draining lymph node post vaccination in rats Frontiers in Immunology innate immune activation magnetic resonance imaging positron emission tomography self-amplifying mRNA lipid nanoparticle AS01 |
| title | MRI/PET multimodal imaging of the innate immune response in skeletal muscle and draining lymph node post vaccination in rats |
| title_full | MRI/PET multimodal imaging of the innate immune response in skeletal muscle and draining lymph node post vaccination in rats |
| title_fullStr | MRI/PET multimodal imaging of the innate immune response in skeletal muscle and draining lymph node post vaccination in rats |
| title_full_unstemmed | MRI/PET multimodal imaging of the innate immune response in skeletal muscle and draining lymph node post vaccination in rats |
| title_short | MRI/PET multimodal imaging of the innate immune response in skeletal muscle and draining lymph node post vaccination in rats |
| title_sort | mri pet multimodal imaging of the innate immune response in skeletal muscle and draining lymph node post vaccination in rats |
| topic | innate immune activation magnetic resonance imaging positron emission tomography self-amplifying mRNA lipid nanoparticle AS01 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1081156/full |
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