| Literature DB >> 34091299 |
Jacob T Martin1, Brittany L Hartwell1, Sidath C Kumarapperuma2, Mariane B Melo1, Diane G Carnathan3, Benjamin J Cossette4, Josetta Adams4, Siqi Gong5, Wei Zhang2, Talar Tokatlian1, Sergey Menis6, Torben Schiffner6, Crystal G Franklin2, Beth Goins2, Peter T Fox2, Guido Silvestri3, William R Schief7, Ruth M Ruprecht8, Darrell J Irvine9.
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.Entities:
Keywords: Fluorescence imaging; HIV; Nanoparticles; Non-human primates; PET imaging; Vaccines
Mesh：
Substances：
Year: 2021 PMID： 34091299 PMCID： PMC8325633 DOI： 10.1016/j.biomaterials.2021.120868
Source DB: PubMed Journal: Biomaterials ISSN： 0142-9612 Impact factor: 12.479