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

doi:10.1016/j.biomaterials.2021.120868

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

Biomaterials. 2021 Aug:275:120868. doi: 10.1016/j.biomaterials.2021.120868. Epub 2021 May 14.

Authors

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

Affiliations

¹ Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, 92037, USA.
² Research Imaging Institute, University of Texas Health San Antonio, San Antonio, TX, 78229, USA.
³ Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, 92037, USA; Yerkes National Primate Research Center, Emory University, Atlanta, GA, 30322, USA; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, 30322, USA.
⁴ Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
⁵ Department of Microbiology, Immunology & Molecular Genetics, University of Texas Health San Antonio, San Antonio, TX, USA; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA.
⁶ Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, 92037, USA; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.
⁷ Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, 92037, USA; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, 92037, USA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, 02139, USA; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, 92037, USA.
⁸ Texas Biomedical Research Institute, San Antonio, TX, 78227, USA; Department of Microbiology, Immunology & Molecular Genetics, University of Texas Health San Antonio, San Antonio, TX, 78229, USA; Department of Biology, University of Louisiana at Lafayette, Lafayette, LA, 70503, USA.
⁹ Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, 92037, USA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, 02139, USA; Departments of Biological Engineering and Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA; Howard Hughes Medical Institute, Chevy Chase, MD, 20815, USA. Electronic address: djirvine@mit.edu.

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.

Keywords: Fluorescence imaging; HIV; Nanoparticles; Non-human primates; PET imaging; Vaccines.

Publication types

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

MeSH terms

AIDS Vaccines*
Adjuvants, Immunologic
Animals
Macaca mulatta
Positron-Emission Tomography
Tissue Distribution
Vaccines*

Substances

AIDS Vaccines
Adjuvants, Immunologic
Vaccines

Abstract

Publication types

MeSH terms

Substances

Grants and funding