Combined PET and whole-tissue imaging of lymphatic-targeting vaccines in non-human primates
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; Menis, Sergey; Schiffner, Torben; Franklin, Crystal G; Goins, Beth; Fox, Peter T; Silvestri, Guido; Schief, William R; Ruprecht, Ruth M; Irvine, Darrell J; ... Show more Show less
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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.
Date issued
2021Department
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 EngineeringJournal
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