Combined PET and whole-tissue imaging of lymphatic-targeting vaccines in non-human primates
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Description
Published version
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8.76 MB
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Author(s)
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
Date Issued
2021
Journal
Biomaterials
Publisher
Elsevier BV
Citation
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.
Version
Final published version
Abstract
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.
MIT Department
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
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.biomaterials.2021.120868
