Antigen-activated dendritic cells ameliorate influenza A infections.
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.
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892-3203, USA.
Kobporn
K
Boonnak
Leatrice
L
Vogel
Marlene
M
Orandle
Daniel
D
Zimmerman
Eyal
E
Talor
Kanta
K
Subbarao
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D000998:Antiviral Agents / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation / Q000821:virology; D024882:Drug Resistance, Viral; D005260:Female; D006801:Humans; D007167:Immunotherapy; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology / Q000502:physiology*; D008168:Lung / Q000473:pathology / Q000821:virology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000628:therapy* / Q000821:virology; D053139:Oseltamivir / Q000494:pharmacology; D010446:Peptide Fragments / Q000276:immunology; D019562:Viral Load; D014779:Virus Replication; D015431:Weight Loss
D000956:Antigens, Viral; D000998:Antiviral Agents; D010446:Peptide Fragments; D053139:Oseltamivir