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

Chiara Nembrini, Armando Stano, Karen Y. Dane, Marie Ballester, André J. Van Der Vlies, Benjamin J. Marsland, Melody A. Swartz, Jeffrey A. Hubbell

Research output: Contribution to journalArticle

126 Citations (Scopus)

Abstract

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 + T-cell 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.

Original languageEnglish
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number44
DOIs
StatePublished - Nov 1 2011
Externally publishedYes

Fingerprint

Nanoparticles
Vaccination
T-Lymphocytes
Antigens
Lung
Ovum
Disulfides
Immunization
Vaccines
Cross-Priming
CD8 Antigens
Subunit Vaccines
Aptitude
Ovalbumin
Cellular Immunity
Dendritic Cells
Human Influenza
Lung Diseases
Immunity
Lymph Nodes

Keywords

  • Adjuvant
  • Antigen conjugation
  • Antigen trafficking
  • Prophylactic
  • T lymphocyte

ASJC Scopus subject areas

  • General

Cite this

Nanoparticle conjugation of antigen enhances cytotoxic T-cell responses in pulmonary vaccination. / Nembrini, Chiara; Stano, Armando; Dane, Karen Y.; Ballester, Marie; Van Der Vlies, André J.; Marsland, Benjamin J.; Swartz, Melody A.; Hubbell, Jeffrey A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 44, 01.11.2011.

Research output: Contribution to journalArticle

Nembrini, Chiara ; Stano, Armando ; Dane, Karen Y. ; Ballester, Marie ; Van Der Vlies, André J. ; Marsland, Benjamin J. ; Swartz, Melody A. ; Hubbell, Jeffrey A. / Nanoparticle conjugation of antigen enhances cytotoxic T-cell responses in pulmonary vaccination. In: Proceedings of the National Academy of Sciences of the United States of America. 2011 ; Vol. 108, No. 44.
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