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

• 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
• Journal Title: BIOMATERIALS
• Volume: Volume 275
• Publisher: ELSEVIER SCI LTD | 2021-06-03, Pages 120868-120868
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.biomaterials.2021.120868
• Subjects: Health Sciences, Immunology; Biology, Microbiology
• Keywords: Science & Technology; Technology; Engineering, Biomedical; Materials Science, Biomaterials; Engineering; Materials Science; Vaccines; HIV; Nanoparticles; PET imaging; Fluorescence imaging; Non-human primates; ANTIBODY-RESPONSES; NODE IMMUNIZATION; DENDRITIC CELLS; INNATE IMMUNITY; MUCOSAL; ANTIGEN; INFLUENZA; TRANSPORT; TRAFFICKING; PARTICULATE

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.