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

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16 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 1 2021
Externally published	Yes

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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

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

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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.

N1 - 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)

PY - 2021/8/1

Y1 - 2021/8/1

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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SN - 0142-9612

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JO - Biomaterials

JF - Biomaterials

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

Abstract

Bibliographical note

Keywords

UN SDGs

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