Antigen delivery to dendritic cells by poly(propylene sulfide) nanoparticles with disulfide conjugated peptides: Cross-presentation and T cell activation

Hirosue, Sachiko; Kourtis, Iraklis C.; Vlies, André J. van der; Hubbell, Jeffrey A.; Swartz, Melody A.

doi:10.1016/j.vaccine.2010.09.077

Cited by 206 publications

(209 citation statements)

References 48 publications

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“…Vaccine formulations against M. tb currently in clinical trials, such as recombinant bacillus Calmette-Guérin, have shown promising outcomes as a result of improved cross-presentation (30). We have previously shown that the chemistry of antigen conjugation to NPs influences cross-presentation and CD8 + T-cell activation (8,31); here, we confirmed that protein conjugation to NPs by disulfide bonds, which are reduced within the endosome after APC uptake, promotes CD8 + T-cell cross-priming, proliferation, and cytokine production in a DC/T-cell coculture.…”

Section: Discussionmentioning

confidence: 99%

“…To this end, we conjugated the model antigen ovalbumin (ova) to our recently described PPS NPs (7) via an endosomally reversible disulfide link, which we demonstrated to be particularly advantageous for driving efficient cross-presentation (8). We administered the NPs in the lungs of mice in combination with the immunostimulatory oligonucleotide CpG as an adjuvant.…”

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confidence: 99%

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Nanoparticle conjugation of antigen enhances cytotoxic T-cell responses in pulmonary vaccination

Nembrini

Stano

Dane

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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The ability of vaccines to induce memory cytotoxic T-cell responses in the lung is crucial in stemming and treating pulmonary diseases caused by viruses and bacteria. However, most approaches to subunit vaccines produce primarily humoral and only to a lesser extent cellular immune responses. We developed a nanoparticle (NP)-based carrier that, upon delivery to the lung, specifically targets pulmonary dendritic cells, thus enhancing antigen uptake and transport to the draining lymph node; antigen coupling via a disulfide link promotes highly efficient cross-presentation after uptake, inducing potent protective mucosal and systemic CD8 + Tcell immunity. Pulmonary immunization with NP-conjugated ovalbumin (NP-ova) with CpG induced a threefold enhancement of splenic antigen-specific CD8 + T cells displaying increased CD107a expression and IFN-γ production compared with immunization with soluble (i.e., unconjugated) ova with CpG. This enhanced response was accompanied by a potent Th17 cytokine profile in CD4 + T cells. After 50 d, NP-ova and CpG also led to substantial enhancements in memory CD8 + T-cell effector functions. Importantly, pulmonary vaccination with NP-ova and CpG induced as much as 10-fold increased frequencies of antigen-specific effector CD8 + T cells to the lung and completely protected mice from morbidity following influenza-ova infection. Here, we highlight recruitment to the lung of a long-lasting pool of protective effector memory cytotoxic T-cells by our disulfide-linked antigen-conjugated NP formulation. These results suggest the reduction-reversible NP system is a highly promising platform for vaccines specifically targeting intracellular pathogens infecting the lung.adjuvant | antigen trafficking | T lymphocyte | prophylactic | antigen conjugation

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Nanoparticle conjugation of antigen enhances cytotoxic T-cell responses in pulmonary vaccination

Nembrini

Stano

Dane

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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161

151

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“…These include particulate and soluble formulations where either the antigen or adjuvant was conjugated with a reversible linker onto either a nanoparticle or a polymer carrier. 8,10,[22][23][24][25][26][27][28] The redoxresponsive disulphide bond was selected as a conjugate linker to achieve triggered release of the antigen from the adjuvant once the soluble conjugate was delivered inside the cell. The disulphide bond can be cleaved through the thiol-disulphide exchange reactions with a redox molecule such as glutathione (GSH), which is found at millimolar concentrations (0.5-10 mM) in intracellular compartments, while its concentration is much lower in extracellular milieu (2-40 mM).…”

Section: Introductionmentioning

confidence: 99%

Intracellular Cleavable CpG Oligodeoxynucleotide-Antigen Conjugate Enhances Anti-tumor Immunity

et al. 2017

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“…Ultrasmall, functionalizable nanoparticles (NP) developed in our laboratory effectively target DCs in skin-draining LNs upon intradermal delivery (20,21). These nanoparticles lead to antigen crosspresentation by DCs and to enhanced cytotoxic antigenspecific CD8 þ T-cell immunity when coupled with an antigen or an adjuvant (22)(23)(24).…”

Section: Introductionmentioning

confidence: 99%

Enhancing Efficacy of Anticancer Vaccines by Targeted Delivery to Tumor-Draining Lymph Nodes

Jeanbart

Ballester

Titta

et al. 2014

Cancer Immunology Research

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The sentinel or tumor-draining lymph node (tdLN) serves as a metastatic niche for many solid tumors and is altered via tumor-derived factors that support tumor progression and metastasis. tdLNs are often removed surgically, and therapeutic vaccines against tumor antigens are typically administered systemically or in nontumor-associated sites. Although the tdLN is immune-suppressed, it is also antigen experienced through drainage of tumor-associated antigens (TAA), so we asked whether therapeutic vaccines targeting the tdLN would be more or less effective than those targeting the non-tdLN. Using LN-targeting nanoparticle (NP)-conjugate vaccines consisting of TAA-NP and CpG-NP, we compared delivery to the tdLN versus non-tdLN in two different cancer models, E.G7-OVA lymphoma (expressing the nonendogenous TAA ovalbumin) and B16-F10 melanoma. Surprisingly, despite the immune-suppressed state of the tdLN, tdLN-targeting vaccination induced substantially stronger cytotoxic CD8 þ T-cell responses, both locally and systemically, than non-tdLN-targeting vaccination, leading to enhanced tumor regression and host survival. This improved tumor regression correlated with a shift in the tumor-infiltrating leukocyte repertoire toward a less suppressive and more immunogenic balance. Nanoparticle coupling of adjuvant and antigen was required for effective tdLN targeting, as nanoparticle coupling dramatically increased the delivery of antigen and adjuvant to LN-resident antigen-presenting cells, thereby increasing therapeutic efficacy. This work highlights the tdLN as a target for cancer immunotherapy and shows how its antigen-experienced but immune-suppressed state can be reprogrammed with a targeted vaccine yielding antitumor immunity. Cancer Immunol Res; 2(5); 436-47. Ó2014 AACR.

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Antigen delivery to dendritic cells by poly(propylene sulfide) nanoparticles with disulfide conjugated peptides: Cross-presentation and T cell activation

Cited by 206 publications

References 48 publications

Nanoparticle conjugation of antigen enhances cytotoxic T-cell responses in pulmonary vaccination

Nanoparticle conjugation of antigen enhances cytotoxic T-cell responses in pulmonary vaccination

Intracellular Cleavable CpG Oligodeoxynucleotide-Antigen Conjugate Enhances Anti-tumor Immunity

Enhancing Efficacy of Anticancer Vaccines by Targeted Delivery to Tumor-Draining Lymph Nodes

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