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Journal of Virology, September 2002, p. 8769-8775, Vol. 76, No. 17
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.17.8769-8775.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Generation of Neutralizing Activity against Human Immunodeficiency Virus Type 1 in Serum by Antibody Gene Transfer

Anne D. Lewis,1 Ruju Chen,1 David C. Montefiori,2 Philip R. Johnson,1,3,4* and K. Reed Clark1,3,4,,

Columbus Children's Research Institute, Children's Hospital,1 Department of Pediatrics,3 Department of Molecular Virology, Immunology, and Medical Genetics, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio,4 Department of Surgery, Duke University Medical Center, Durham, North Carolina2

Received 5 February 2002/ Accepted 28 May 2002

Although several human immunodeficiency virus (HIV) vaccine approaches have elicited meaningful antigen-specific T-cell responses in animal models, no single vaccine candidate has engendered antibodies that broadly neutralize primary isolates of HIV type 1 (HIV-1). Thus, there remains a significant gap in the design of HIV vaccines. To address this issue, we exploited the existence of rare human monoclonal antibodies that have been isolated from HIV-infected individuals. Such antibodies neutralize a wide array of HIV-1 field isolates and have been shown to be effective in vivo. However, practical considerations preclude the use of antibody preparations as a prophylactic passive immunization strategy in large populations. Our concept calls for an antibody gene of choice to be transferred to muscle where the antibody molecule is synthesized and distributed to the circulatory system. In these experiments, we used a recombinant adeno-associated virus (rAAV) vector to deliver the gene for the human antibody IgG1b12 to mouse muscle. Significant levels of HIV-neutralizing activity were found in the sera of mice for over 6 months after a single intramuscular administration of the rAAV vector. This approach allows for predetermination of antibody affinity and specificity prior to "immunization" and avoids the need for an active humoral immune response against the HIV envelope protein.

* Corresponding author. Mailing address: Rm. W591, Children's Research Institute, 700 Children's Dr., Columbus, OH 43205. Phone: (614) 722-2735. Fax: (614) 722-3273. E-mail: johnsonp{at}pediatrics.ohio-state.edu.

{dagger} Present address: Department of Pathology, Oregon Regional Primate Research Center, Beaverton, OR 97006.

Journal of Virology, September 2002, p. 8769-8775, Vol. 76, No. 17
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.17.8769-8775.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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