Combined PET and whole-tissue imaging of lymphatic-targeting vaccines in non-human primates
Antigen accumulation in lymph nodes (LNs) is critical for vaccine efficacy, but understanding of vaccine biodistribution in humans or large animals remains limited. Using the rhesus macaque model, we employed a combination of positron emission tomography (PET) and fluorescence imaging to characteriz...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier BV
2021
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| Online Access: | https://hdl.handle.net/1721.1/133108 |
| _version_ | 1826196453832261632 |
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| author | Martin, Jacob T Hartwell, Brittany L Kumarapperuma, Sidath C Melo, Mariane B Carnathan, Diane G Cossette, Benjamin J Adams, Josetta Gong, Siqi Zhang, Wei Tokatlian, Talar Menis, Sergey Schiffner, Torben Franklin, Crystal G Goins, Beth Fox, Peter T Silvestri, Guido Schief, William R Ruprecht, Ruth M Irvine, Darrell J |
| author2 | Koch Institute for Integrative Cancer Research at MIT |
| author_facet | Koch Institute for Integrative Cancer Research at MIT Martin, Jacob T Hartwell, Brittany L Kumarapperuma, Sidath C Melo, Mariane B Carnathan, Diane G Cossette, Benjamin J Adams, Josetta Gong, Siqi Zhang, Wei Tokatlian, Talar Menis, Sergey Schiffner, Torben Franklin, Crystal G Goins, Beth Fox, Peter T Silvestri, Guido Schief, William R Ruprecht, Ruth M Irvine, Darrell J |
| author_sort | Martin, Jacob T |
| collection | MIT |
| description | Antigen accumulation in lymph nodes (LNs) is critical for vaccine efficacy, but understanding of vaccine biodistribution in humans or large animals remains limited. Using the rhesus macaque model, we employed a combination of positron emission tomography (PET) and fluorescence imaging to characterize the whole-animal to tissue-level biodistribution of a subunit vaccine comprised of an HIV envelope trimer protein nanoparticle (trimer-NP) and lipid-conjugated CpG adjuvant (amph-CpG). Following immunization in the thigh, PET imaging revealed vaccine uptake primarily in inguinal and iliac LNs, reaching distances up to 17 cm away from the injection site. Within LNs, trimer-NPs exhibited striking accumulation on the periphery of follicular dendritic cell (FDC) networks in B cell follicles. Comparative imaging of soluble Env trimers (not presented on nanoparticles) in naïve or previously-immunized animals revealed diffuse deposition of trimer antigens in LNs following primary immunization, but concentration on FDCs in pre-immunized animals with high levels of trimer-specific IgG. These data demonstrate the capacity of nanoparticle or "albumin hitchhiking" technologies to concentrate vaccines in genitourinary tract-draining LNs, which may be valuable for promoting mucosal immunity. |
| first_indexed | 2024-09-23T10:26:46Z |
| format | Article |
| id | mit-1721.1/133108 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T10:26:46Z |
| publishDate | 2021 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1331082023-07-28T20:19:05Z Combined PET and whole-tissue imaging of lymphatic-targeting vaccines in non-human primates Martin, Jacob T Hartwell, Brittany L Kumarapperuma, Sidath C Melo, Mariane B Carnathan, Diane G Cossette, Benjamin J Adams, Josetta Gong, Siqi Zhang, Wei Tokatlian, Talar Menis, Sergey Schiffner, Torben Franklin, Crystal G Goins, Beth Fox, Peter T Silvestri, Guido Schief, William R Ruprecht, Ruth M Irvine, Darrell J Koch Institute for Integrative Cancer Research at MIT Ragon Institute of MGH, MIT and Harvard Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Materials Science and Engineering Antigen accumulation in lymph nodes (LNs) is critical for vaccine efficacy, but understanding of vaccine biodistribution in humans or large animals remains limited. Using the rhesus macaque model, we employed a combination of positron emission tomography (PET) and fluorescence imaging to characterize the whole-animal to tissue-level biodistribution of a subunit vaccine comprised of an HIV envelope trimer protein nanoparticle (trimer-NP) and lipid-conjugated CpG adjuvant (amph-CpG). Following immunization in the thigh, PET imaging revealed vaccine uptake primarily in inguinal and iliac LNs, reaching distances up to 17 cm away from the injection site. Within LNs, trimer-NPs exhibited striking accumulation on the periphery of follicular dendritic cell (FDC) networks in B cell follicles. Comparative imaging of soluble Env trimers (not presented on nanoparticles) in naïve or previously-immunized animals revealed diffuse deposition of trimer antigens in LNs following primary immunization, but concentration on FDCs in pre-immunized animals with high levels of trimer-specific IgG. These data demonstrate the capacity of nanoparticle or "albumin hitchhiking" technologies to concentrate vaccines in genitourinary tract-draining LNs, which may be valuable for promoting mucosal immunity. 2021-10-25T18:34:26Z 2021-10-25T18:34:26Z 2021 2021-09-03T17:34:04Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/133108 Martin, Jacob T, Hartwell, Brittany L, Kumarapperuma, Sidath C, Melo, Mariane B, Carnathan, Diane G et al. 2021. "Combined PET and whole-tissue imaging of lymphatic-targeting vaccines in non-human primates." Biomaterials, 275. en 10.1016/j.biomaterials.2021.120868 Biomaterials Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV Elsevier |
| spellingShingle | Martin, Jacob T Hartwell, Brittany L Kumarapperuma, Sidath C Melo, Mariane B Carnathan, Diane G Cossette, Benjamin J Adams, Josetta Gong, Siqi Zhang, Wei Tokatlian, Talar Menis, Sergey Schiffner, Torben Franklin, Crystal G Goins, Beth Fox, Peter T Silvestri, Guido Schief, William R Ruprecht, Ruth M Irvine, Darrell J Combined PET and whole-tissue imaging of lymphatic-targeting vaccines in non-human primates |
| title | Combined PET and whole-tissue imaging of lymphatic-targeting vaccines in non-human primates |
| title_full | Combined PET and whole-tissue imaging of lymphatic-targeting vaccines in non-human primates |
| title_fullStr | Combined PET and whole-tissue imaging of lymphatic-targeting vaccines in non-human primates |
| title_full_unstemmed | Combined PET and whole-tissue imaging of lymphatic-targeting vaccines in non-human primates |
| title_short | Combined PET and whole-tissue imaging of lymphatic-targeting vaccines in non-human primates |
| title_sort | combined pet and whole tissue imaging of lymphatic targeting vaccines in non human primates |
| url | https://hdl.handle.net/1721.1/133108 |
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