Combined PET and whole-tissue imaging of lymphatic-targeting vaccines in non-human primates

• Type of Material: Article
• Authors: Jacob T Martin, Massachusetts Institute of Technology; Brittany L Hartwell, Massachusetts Institute of Technology; Sidath C Kumarapperuma, University of Texas Health San Antonio; Mariane B Melo, Massachusetts Institute of Technology; Diane G Carnathan, Scripps Research Institute; Benjamin J Cossette, Massachusetts Institute of Technology; Josetta Adams, Massachusetts Institute of Technology; Siqi Gong, University of Texas Health San Antonio; Wei Zhang, University of Texas Health San Antonio; Talar Tokatlian, Massachusetts Institute of Technology; Sergey Menis, Scripps Research Institute; Torben Schiffner, Scripps Research Institute; Crystal G Franklin, University of Texas Health San Antonio; Beth Goins, University of Texas Health San Antonio; Peter T Fox, University of Texas Health San Antonio; Guido Silvestri, Emory University; William R Schief, Scripps Research Institute; Ruth M Ruprecht, Texas Biomedical Research Institute; Darrell J Irvine, Massachusetts Institute of Technology
• Language: English
• Date: 2021-06-03
• Publisher: ELSEVIER SCI LTD
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2021 The Author(s). Published by Elsevier Ltd.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.biomaterials.2021.120868
• Title of Journal or Parent Work: BIOMATERIALS
• Volume: 275
• Start Page: 120868
• End Page: 120868
• Grant/Funding Information: This work was supported by the NIH (award P01AI048240 to RMR, SCK, PTF, and DJI, award UM1 AI144462 to DJI and WRS), the Ragon Institute of MGH, MIT, and Harvard, the U. S. Army Research Office through the Institute for Soldier Nanotechnologies at MIT, under Cooperative Agreement Number W911NF-18-2-0048, and the Koch Institute Support (core) Grant P30-CA14051.
• Keywords: TRAFFICKING; Materials Science; PARTICULATE; TRANSPORT; ANTIGEN; Nanoparticles; INFLUENZA; INNATE IMMUNITY; ANTIBODY-RESPONSES; Engineering; NODE IMMUNIZATION; Technology; DENDRITIC CELLS; Science & Technology; PET imaging; Non-human primates; MUCOSAL; Engineering, Biomedical; Materials Science, Biomaterials; Fluorescence imaging; Vaccines; HIV

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.