Specific Depletion of Human Anti-Adenovirus Antibodies Facilitates Transduction in an in Vivo Model for Systemic Gene Therapy

Molecular Therapy, Vol. 3, Issue 5, May 2001

Posted: 19 Apr 2018

See all articles by Amena Rahman

Amena Rahman

Canji, Inc. - Department of Molecular Biology

Van Tsai

Canji, Inc. - Department of Pharmacology

Ann Goudreau

Canji, Inc. - Department of Molecular Biology

Jeremy Shinoda

Cordant Health Solutions

Shu Fen Wen

Canji, Inc. - Department of Process Sciences

Muralidhara Ramachandra

Canji, Inc. - Department of Molecular Biology

Rob Ralston

Canji, Inc. - Department of Molecular Biology

Dan Maneval

Canji, Inc. - Department of Pharmacology

Drake LaFace

Canji, Inc. - Department of Pharmacology

Paul Shabram

Canji, Inc. - Department of Process Sciences

Date Written: March 22, 2001

Abstract

Recombinant adenoviral (rAd) vectors are capable of mediating high-efficiency gene transfer in vivo. Under conditions requiring systemic administration, however, the use of rAd vectors can be problematic due to the presence of circulating anti-adenovirus antibodies developed either through natural infection or during the course of treatment. We developed a passive immunization model in SCID/Beige mice to assess the effect of human and mouse anti-adenovirus antibodies on systemic administration of a rAd vector expressing β-galactosidase (rAd-βgal). In this model, the in vitro neutralizing activity of human or mouse antibodies used for passive immunization correlated well with inhibition of transduction of the liver following i.v. administration of rAd-βgal. Depletion of antibodies to individual adenovirus structural proteins (hexon, penton, fiber) by affinity chromatography demonstrated that antibodies to each of the three virion components contributed to neutralization of infectivity in vitro and to inhibition of transduction in vivo. Depletion of antibodies against all three structural proteins from human or mouse immune serum prior to passive immunization restored in vivo transduction activity to levels comparable to those obtained with nonimmune serum. Our data suggest that depletion of both murine and human anti-adenoviral antibodies can restore transduction in vivo during systemic rAd gene therapy in hosts previously exposed to adenovirus.

Keywords: recombinant adenovirus, neutralizing antibodies, capsid columns, immunopheresis, transduction efficiency, β-galactosidase rAd-vector, empty rAd-vector, green fluorescent protein rAd-vector, depletion

Suggested Citation

Rahman, Amena and Tsai, Van and Goudreau, Ann and Shinoda, Jeremy and Wen, Shu Fen and Ramachandra, Muralidhara and Ralston, Rob and Maneval, Dan and LaFace, Drake and Shabram, Paul, Specific Depletion of Human Anti-Adenovirus Antibodies Facilitates Transduction in an in Vivo Model for Systemic Gene Therapy (March 22, 2001). Molecular Therapy, Vol. 3, Issue 5, May 2001. Available at SSRN: https://ssrn.com/abstract=3150454

Amena Rahman

Canji, Inc. - Department of Molecular Biology

CA 92121
United States

Van Tsai

Canji, Inc. - Department of Pharmacology

CA 92121
United States

Ann Goudreau

Canji, Inc. - Department of Molecular Biology

CA 92121
United States

Jeremy Shinoda (Contact Author)

Cordant Health Solutions ( email )

United States

HOME PAGE: http://www.cordantsolutions.com

Shu Fen Wen

Canji, Inc. - Department of Process Sciences

CA 92121
United States

Muralidhara Ramachandra

Canji, Inc. - Department of Molecular Biology

CA 92121
United States

Rob Ralston

Canji, Inc. - Department of Molecular Biology

CA 92121
United States

Dan Maneval

Canji, Inc. - Department of Pharmacology

CA 92121
United States

Drake LaFace

Canji, Inc. - Department of Pharmacology

CA 92121
United States

Paul Shabram

Canji, Inc. - Department of Process Sciences ( email )

CA 92121
United States

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