{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:32:57Z","timestamp":1791318777657,"version":"4.3.1"},"reference-count":43,"publisher":"National Academy of Sciences","issue":"44","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,11]]},"abstract":"<jats:p>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    T-cell immunity. Pulmonary immunization with NP-conjugated ovalbumin (NP-ova) with CpG induced a threefold enhancement of splenic antigen-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells displaying increased CD107a expression and IFN-\u03b3 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\n                    <jats:sup>+<\/jats:sup>\n                    T cells. After 50 d, NP-ova and CpG also led to substantial enhancements in memory CD8\n                    <jats:sup>+<\/jats:sup>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1104264108","type":"journal-article","created":{"date-parts":[[2011,10,4]],"date-time":"2011-10-04T00:09:41Z","timestamp":1317686981000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":165,"title":["Nanoparticle conjugation of antigen enhances cytotoxic T-cell responses in pulmonary vaccination"],"prefix":"10.1073","volume":"108","author":[{"given":"Chiara","family":"Nembrini","sequence":"first","affiliation":[{"name":"Laboratory for Regenerative Medicine and Pharmacobiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armando","family":"Stano","sequence":"additional","affiliation":[{"name":"Laboratory for Regenerative Medicine and Pharmacobiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen Y.","family":"Dane","sequence":"additional","affiliation":[{"name":"Laboratory for Regenerative Medicine and Pharmacobiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Ballester","sequence":"additional","affiliation":[{"name":"Laboratory for Regenerative Medicine and Pharmacobiology and"},{"name":"Laboratory of Lymphatic and Cancer Bioengineering, Institute of Bioengineering, Ecole Polytechnique F\u00e9d\u00e9rale Lausanne, CH-1015 Lausanne, Switzerland; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 J.","family":"van der Vlies","sequence":"additional","affiliation":[{"name":"Laboratory for Regenerative Medicine and Pharmacobiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin J.","family":"Marsland","sequence":"additional","affiliation":[{"name":"Division of Pneumology, Centre Hospitalier Universitaire 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