Recombinant Adenovirus Vectors Activate the Alternative Complement Pathway, Leading to the Binding of Human Complement Protein C3 Independent of Anti-Ad Antibodies

doi:doi:10.1016/j.ymthe.2004.08.015

Molecular Therapy (2004) 10, 1140–1142; doi: 10.1016/j.ymthe.2004.08.015

Recombinant Adenovirus Vectors Activate the Alternative Complement Pathway, Leading to the Binding of Human Complement Protein C3 Independent of Anti-Ad Antibodies

H. Jiang¹, Z. Wang¹, D. Serra¹, M. M. Frank¹ and A. Amalfitano¹

¹Department of Pediatrics, Department of Pathology, Department of Molecular Genetics, and Department of Microbiology, Duke University Medical Center, Durham, NC 27710, USA

Correspondence: A. Amalfitano, Departments of Pediatrics, Pathology, Molecular Genetics, and Microbiology, Box 2618, Room 101B, MSRB, Duke University Medical Center, Durham, NC 27710, USA. Fax: +919 684 2362. E-mail: amalf001@mc.duke.edu

Received 15 March 2004; Accepted 23 August 2004.

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Abstract

Recombinant adenoviruses are one of the most common gene transfer vectors utilized in human clinical trials, but it is also clear that systemic administration of this virus will be met by host innate and adaptive antiviral immune responses. One element of innate immunity is the complement system, a group of proteins that has evolved to rapidly recognize foreign microbes and viruses and to clear them from the circulatory system prior to their gaining entry to vulnerable host cells. Excessive complement activation can initiate or propagate a number of deleterious inflammatory responses, by release of potent cytokines and anaphylatoxins and/or by direct cellular toxicity. These reactions can progress rapidly and are factors important in serious complications, including the systemic inflammatory response syndrome and the adult respiratory distress syndrome.