tetano
Editor, Senior Moderator
J Clin Invest. doi:10.1172/JCI67550.
Copyright ? 2013, The American Society for Clinical Investigation.
Research Article
Antigen-activated dendritic cells ameliorate influenza A infections
Kobporn Boonnak1, Leatrice Vogel1, Marlene Orandle2, Daniel Zimmerman3, Eyal Talor3 and Kanta Subbarao1
1Laboratory of Infectious Diseases and
2Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA.
3CEL-SCI Corp., Vienna, Virginia, USA.
Address correspondence to: Kanta Subbarao, Emerging Respiratory Viruses Section, Laboratory of Infectious Diseases, NIAID, NIH, Bldg. 33, Room 3E13C.1, 33 North Drive, MSC 3203, Bethesda, Maryland 20892-3203, USA. Phone: 301.451.3839; Fax: 301.480.4749; E-mail: KSUBBARAO@niaid.nih.gov.
Published June 24, 2013
Received for publication October 26, 2012, and accepted in revised form April 11, 2013.
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.
full article
http://www.jci.org/articles/view/67550
Copyright ? 2013, The American Society for Clinical Investigation.
Research Article
Antigen-activated dendritic cells ameliorate influenza A infections
Kobporn Boonnak1, Leatrice Vogel1, Marlene Orandle2, Daniel Zimmerman3, Eyal Talor3 and Kanta Subbarao1
1Laboratory of Infectious Diseases and
2Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA.
3CEL-SCI Corp., Vienna, Virginia, USA.
Address correspondence to: Kanta Subbarao, Emerging Respiratory Viruses Section, Laboratory of Infectious Diseases, NIAID, NIH, Bldg. 33, Room 3E13C.1, 33 North Drive, MSC 3203, Bethesda, Maryland 20892-3203, USA. Phone: 301.451.3839; Fax: 301.480.4749; E-mail: KSUBBARAO@niaid.nih.gov.
Published June 24, 2013
Received for publication October 26, 2012, and accepted in revised form April 11, 2013.
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.
full article
http://www.jci.org/articles/view/67550