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 2021

Keywords

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

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Ceramics and Composites
  • Biomaterials
  • Mechanics of Materials

Fingerprint

Dive into the research topics of 'Combined PET and whole-tissue imaging of lymphatic-targeting vaccines in non-human primates'. Together they form a unique fingerprint.

Cite this