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

Jacob T. Martin, Brittany L. Hartwell, Sidath C. Kumarapperuma, Mariane B. Melo, Diane G. Carnathan, Benjamin J. Cossette, Josetta Adams, Siqi Gong, Wei Zhang, Talar Tokatlian, Sergey Menis, Torben Schiffner, Crystal G. Franklin, Beth Goins, Peter T. Fox, Guido Silvestri, William R. Schief, Ruth M. Ruprecht, Darrell J. Irvine

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number120868
JournalBiomaterials
Volume275
DOIs
StatePublished - Aug 1 2021
Externally publishedYes

Bibliographical note

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 .

Publisher Copyright:
© 2021 The Author(s)

Keywords

  • Fluorescence imaging
  • HIV
  • Nanoparticles
  • Non-human primates
  • PET imaging
  • Vaccines

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

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