Antigen-activated dendritic cells ameliorate influenza A infections
Kobporn Boonnak, … , Eyal Talor, Kanta Subbarao
Kobporn Boonnak, … , Eyal Talor, Kanta Subbarao
Published June 24, 2013
Citation Information: J Clin Invest. 2013;123(7):2850-2861. https://doi.org/10.1172/JCI67550.
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Antigen-activated dendritic cells ameliorate influenza A infections

Abstract

Influenza A viruses cause significant morbidity and mortality worldwide. There is a need for alternative or adjunct therapies, as resistance to currently used antiviral drugs is emerging rapidly. We tested ligand epitope antigen presentation system (LEAPS) technology as a new immune-based treatment for influenza virus infection in a mouse model. Influenza-J-LEAPS peptides were synthesized by conjugating the binding ligand derived from the β2-microglobulin chain of the human MHC class I molecule (J-LEAPS) with 15 to 30 amino acid–long peptides derived from influenza virus NP, M, or HA proteins. DCs were stimulated with influenza-J-LEAPS peptides (influenza-J-LEAPS) and injected intravenously into infected mice. Antigen-specific LEAPS-stimulated DCs were effective in reducing influenza virus replication in the lungs and enhancing survival of infected animals. Additionally, they augmented influenza-specific T cell responses in the lungs and reduced the severity of disease by limiting excessive cytokine responses, which are known to contribute to morbidity and mortality following influenza virus infection. Our data demonstrate that influenza-J-LEAPS–pulsed DCs reduce virus replication in the lungs, enhance survival, and modulate the protective immune responses that eliminate the virus while preventing excessive cytokines that could injure the host. This approach shows promise as an adjunct to antiviral treatment of influenza virus infections.

Authors

Kobporn Boonnak, Leatrice Vogel, Marlene Orandle, Daniel Zimmerman, Eyal Talor, Kanta Subbarao

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Figure 2

LEAPS-loaded DCs target the site of infection.

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LEAPS-loaded DCs target the site of infection. 107 CFSE-labeled nonpulse...
107 CFSE-labeled nonpulsed DCs, JH-LEAPS–pulsed DCs (irrelevant LEAPS control), or combined-LEAPS–pulsed DCs were injected i.v. into naive mice (A) or influenza virus–infected mice (10 LD50, PR8 virus, i.n.) (B). The accumulation of CFSE-positive cells was measured in the lungs of mice 8, 24, and 48 hours after administration of the LEAPS-stimulated DCs. The data are representative FACS plots from each group (n = 5 mice/group).