Generation of neutralizing activity against human immunodeficiency virus type 1 in serum by antibody gene transfer.
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.
Lewis
Anne D
AD
Columbus Children's Research Institute, Children's Hospital, Department of Pediatrics, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio, USA.
Chen
Ruju
R
Montefiori
David C
DC
Johnson
Philip R
PR
Clark
K Reed
KR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood / Q000235:genetics / Q000276:immunology; D000229:Dependovirus / Q000235:genetics*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage*; D015483:HIV Antibodies / Q000008:administration & dosage / Q000097:blood / Q000235:genetics / Q000276:immunology; D019302:HIV Envelope Protein gp160 / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007273:Injections, Intramuscular; D051379:Mice; D018482:Muscle, Skeletal / Q000276:immunology; D009500:Neutralization Tests; D011995:Recombination, Genetic; D014161:Transduction, Genetic
D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D019302:HIV Envelope Protein gp160; D007074:Immunoglobulin G