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

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 journal › Article › peer-review

22 Scopus citations

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 language	English (US)
Article number	120868
Journal	Biomaterials
Volume	275
DOIs	https://doi.org/10.1016/j.biomaterials.2021.120868
State	Published - Aug 2021

Keywords

Fluorescence imaging
HIV
Nanoparticles
Non-human primates
PET imaging
Vaccines

ASJC Scopus subject areas

Mechanics of Materials
Ceramics and Composites
Bioengineering
Biophysics
Biomaterials

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10.1016/j.biomaterials.2021.120868

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Martin, J. T., Hartwell, B. L., Kumarapperuma, S. C., Melo, M. B., Carnathan, D. G., Cossette, B. J., Adams, J., Gong, S., Zhang, W., Tokatlian, T., Menis, S., Schiffner, T., Franklin, C. G., Goins, B., Fox, P. T., Silvestri, G., Schief, W. R., Ruprecht, R. M., & Irvine, D. J. (2021). Combined PET and whole-tissue imaging of lymphatic-targeting vaccines in non-human primates. Biomaterials, 275, Article 120868. https://doi.org/10.1016/j.biomaterials.2021.120868

Martin, JT, Hartwell, BL, Kumarapperuma, SC, Melo, MB, Carnathan, DG, Cossette, BJ, Adams, J, Gong, S, Zhang, W, Tokatlian, T, Menis, S, Schiffner, T, Franklin, CG, Goins, B, Fox, PT, Silvestri, G, Schief, WR, Ruprecht, RM & Irvine, DJ 2021, 'Combined PET and whole-tissue imaging of lymphatic-targeting vaccines in non-human primates', Biomaterials, vol. 275, 120868. https://doi.org/10.1016/j.biomaterials.2021.120868

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title = "Combined PET and whole-tissue imaging of lymphatic-targeting vaccines in non-human primates",

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 na{\"i}ve 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",

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

note = "Publisher Copyright: {\textcopyright} 2021 The Author(s)",

year = "2021",

month = aug,

doi = "10.1016/j.biomaterials.2021.120868",

language = "English (US)",

volume = "275",

journal = "Biomaterials",

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T1 - Combined PET and whole-tissue imaging of lymphatic-targeting vaccines in non-human primates

AU - Martin, Jacob T.

AU - Hartwell, Brittany L.

AU - Kumarapperuma, Sidath C.

AU - Melo, Mariane B.

AU - Carnathan, Diane G.

AU - Cossette, Benjamin J.

AU - Adams, Josetta

AU - Gong, Siqi

AU - Zhang, Wei

AU - Tokatlian, Talar

AU - Menis, Sergey

AU - Schiffner, Torben

AU - Franklin, Crystal G.

AU - Goins, Beth

AU - Fox, Peter T.

AU - Silvestri, Guido

AU - Schief, William R.

AU - Ruprecht, Ruth M.

AU - Irvine, Darrell J.

PY - 2021/8

Y1 - 2021/8

N2 - 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.

AB - 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.

KW - Fluorescence imaging

KW - HIV

KW - Nanoparticles

KW - Non-human primates

KW - PET imaging

KW - Vaccines

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JO - Biomaterials

JF - Biomaterials

M1 - 120868

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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