Tunable T cell immunity towards a protein antigen using polymersomes vs. solid-core nanoparticles

Armando Stano, Evan A. Scott, Karen Y. Dane, Melody A. Swartz, Jeffrey A. Hubbell

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Using poly(propylene sulfide) (PPS) and poly(ethylene glycol) (PEG) as components of a nanocarrier platform, we sought to compare immune responses induced by PPS-bl-PEG polymersomes (PSs; watery-core structures, with antigen incorporated within the PSs) and PEG-stabilized PPS nanoparticles (NPs; solid-core structures, with antigen conjugated upon the NP surface). We have previously shown strong CD8+ T cell responses to antigen conjugated to NPs via a disulfide link, and here we investigated the extent to which antigen incorporated within oxidatively-sensitive PSs could induce CD4+ or CD8+ T cell responses. C57BL/6 mice were subcutaneously immunized with free ovalbumin (OVA) as a model antigen, or equivalent doses of OVA-loaded into PSs, conjugated onto NPs, or given as a mixture of the two. Free CpG was used as an adjuvant. Antigen-loaded PSs induced enhanced frequencies of antigen-specific CD4+ T cells in the spleen, lymph nodes and lungs as compared to the NP formulation, whereas antigen-conjugated NPs induced stronger CD8+ T cell responses. Co-administration of both PSs and NPs elicited T cell immunity characteristic of the two nanocarriers at the same time, i.e. both strong CD4+ and CD8+ T cell responses. These results have important implications for particulate-based vaccine design and highlight the potential of using different antigen-delivery systems for the induction of both T helper and cytotoxic T lymphocyte immune responses.

Original languageEnglish
Pages (from-to)4339-4346
Number of pages8
JournalBiomaterials
Volume34
Issue number17
DOIs
StatePublished - Jun 1 2013
Externally publishedYes

Fingerprint

T-cells
Antigens
Nanoparticles
Immunity
Proteins
T-Lymphocytes
Ethylene Glycol
Polyethylene glycols
Ovalbumin
Propylene
CD4 Antigens
Cytotoxic T-Lymphocytes
Vaccines
Helper-Inducer T-Lymphocytes
Inbred C57BL Mouse
Disulfides
Spleen
Polypropylenes
Lymph Nodes
Lung

Keywords

  • Flow cytometry
  • Immune response
  • Immunomodulation
  • Immunostimulation
  • Nanoparticle

ASJC Scopus subject areas

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

Cite this

Tunable T cell immunity towards a protein antigen using polymersomes vs. solid-core nanoparticles. / Stano, Armando; Scott, Evan A.; Dane, Karen Y.; Swartz, Melody A.; Hubbell, Jeffrey A.

In: Biomaterials, Vol. 34, No. 17, 01.06.2013, p. 4339-4346.

Research output: Contribution to journalArticle

Stano, Armando ; Scott, Evan A. ; Dane, Karen Y. ; Swartz, Melody A. ; Hubbell, Jeffrey A. / Tunable T cell immunity towards a protein antigen using polymersomes vs. solid-core nanoparticles. In: Biomaterials. 2013 ; Vol. 34, No. 17. pp. 4339-4346.
@article{a07d1688f229485791f8a68949cde634,
title = "Tunable T cell immunity towards a protein antigen using polymersomes vs. solid-core nanoparticles",
abstract = "Using poly(propylene sulfide) (PPS) and poly(ethylene glycol) (PEG) as components of a nanocarrier platform, we sought to compare immune responses induced by PPS-bl-PEG polymersomes (PSs; watery-core structures, with antigen incorporated within the PSs) and PEG-stabilized PPS nanoparticles (NPs; solid-core structures, with antigen conjugated upon the NP surface). We have previously shown strong CD8+ T cell responses to antigen conjugated to NPs via a disulfide link, and here we investigated the extent to which antigen incorporated within oxidatively-sensitive PSs could induce CD4+ or CD8+ T cell responses. C57BL/6 mice were subcutaneously immunized with free ovalbumin (OVA) as a model antigen, or equivalent doses of OVA-loaded into PSs, conjugated onto NPs, or given as a mixture of the two. Free CpG was used as an adjuvant. Antigen-loaded PSs induced enhanced frequencies of antigen-specific CD4+ T cells in the spleen, lymph nodes and lungs as compared to the NP formulation, whereas antigen-conjugated NPs induced stronger CD8+ T cell responses. Co-administration of both PSs and NPs elicited T cell immunity characteristic of the two nanocarriers at the same time, i.e. both strong CD4+ and CD8+ T cell responses. These results have important implications for particulate-based vaccine design and highlight the potential of using different antigen-delivery systems for the induction of both T helper and cytotoxic T lymphocyte immune responses.",
keywords = "Flow cytometry, Immune response, Immunomodulation, Immunostimulation, Nanoparticle",
author = "Armando Stano and Scott, {Evan A.} and Dane, {Karen Y.} and Swartz, {Melody A.} and Hubbell, {Jeffrey A.}",
year = "2013",
month = "6",
day = "1",
doi = "10.1016/j.biomaterials.2013.02.024",
language = "English",
volume = "34",
pages = "4339--4346",
journal = "Biomaterials",
issn = "0142-9612",
publisher = "Elsevier BV",
number = "17",

}

TY - JOUR

T1 - Tunable T cell immunity towards a protein antigen using polymersomes vs. solid-core nanoparticles

AU - Stano, Armando

AU - Scott, Evan A.

AU - Dane, Karen Y.

AU - Swartz, Melody A.

AU - Hubbell, Jeffrey A.

PY - 2013/6/1

Y1 - 2013/6/1

N2 - Using poly(propylene sulfide) (PPS) and poly(ethylene glycol) (PEG) as components of a nanocarrier platform, we sought to compare immune responses induced by PPS-bl-PEG polymersomes (PSs; watery-core structures, with antigen incorporated within the PSs) and PEG-stabilized PPS nanoparticles (NPs; solid-core structures, with antigen conjugated upon the NP surface). We have previously shown strong CD8+ T cell responses to antigen conjugated to NPs via a disulfide link, and here we investigated the extent to which antigen incorporated within oxidatively-sensitive PSs could induce CD4+ or CD8+ T cell responses. C57BL/6 mice were subcutaneously immunized with free ovalbumin (OVA) as a model antigen, or equivalent doses of OVA-loaded into PSs, conjugated onto NPs, or given as a mixture of the two. Free CpG was used as an adjuvant. Antigen-loaded PSs induced enhanced frequencies of antigen-specific CD4+ T cells in the spleen, lymph nodes and lungs as compared to the NP formulation, whereas antigen-conjugated NPs induced stronger CD8+ T cell responses. Co-administration of both PSs and NPs elicited T cell immunity characteristic of the two nanocarriers at the same time, i.e. both strong CD4+ and CD8+ T cell responses. These results have important implications for particulate-based vaccine design and highlight the potential of using different antigen-delivery systems for the induction of both T helper and cytotoxic T lymphocyte immune responses.

AB - Using poly(propylene sulfide) (PPS) and poly(ethylene glycol) (PEG) as components of a nanocarrier platform, we sought to compare immune responses induced by PPS-bl-PEG polymersomes (PSs; watery-core structures, with antigen incorporated within the PSs) and PEG-stabilized PPS nanoparticles (NPs; solid-core structures, with antigen conjugated upon the NP surface). We have previously shown strong CD8+ T cell responses to antigen conjugated to NPs via a disulfide link, and here we investigated the extent to which antigen incorporated within oxidatively-sensitive PSs could induce CD4+ or CD8+ T cell responses. C57BL/6 mice were subcutaneously immunized with free ovalbumin (OVA) as a model antigen, or equivalent doses of OVA-loaded into PSs, conjugated onto NPs, or given as a mixture of the two. Free CpG was used as an adjuvant. Antigen-loaded PSs induced enhanced frequencies of antigen-specific CD4+ T cells in the spleen, lymph nodes and lungs as compared to the NP formulation, whereas antigen-conjugated NPs induced stronger CD8+ T cell responses. Co-administration of both PSs and NPs elicited T cell immunity characteristic of the two nanocarriers at the same time, i.e. both strong CD4+ and CD8+ T cell responses. These results have important implications for particulate-based vaccine design and highlight the potential of using different antigen-delivery systems for the induction of both T helper and cytotoxic T lymphocyte immune responses.

KW - Flow cytometry

KW - Immune response

KW - Immunomodulation

KW - Immunostimulation

KW - Nanoparticle

UR - http://www.scopus.com/inward/record.url?scp=84875553460&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875553460&partnerID=8YFLogxK

U2 - 10.1016/j.biomaterials.2013.02.024

DO - 10.1016/j.biomaterials.2013.02.024

M3 - Article

C2 - 23478034

AN - SCOPUS:84875553460

VL - 34

SP - 4339

EP - 4346

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

IS - 17

ER -