title: Vector-mediated gene transfer engenders long-lived neutralizing activity and protection against SIV infection in monkeys.
abstract: The key to an effective HIV vaccine is development of an immunogen that elicits persisting antibodies with broad neutralizing activity against field strains of the virus. Unfortunately, very little progress has been made in finding or designing such immunogens. Using the simian immunodeficiency virus (SIV) model, we have taken a markedly different approach: delivery to muscle of an adeno-associated virus gene transfer vector expressing antibodies or antibody-like immunoadhesins having predetermined SIV specificity. With this approach, SIV-specific molecules are endogenously synthesized in myofibers and passively distributed to the circulatory system. Using such an approach in monkeys, we have now generated long-lasting neutralizing activity in serum and have observed complete protection against intravenous challenge with virulent SIV. In essence, this strategy bypasses the adaptive immune system and holds considerable promise as a unique approach to an effective HIV vaccine.
authors.affiliation: The Children's Hospital of Philadelphia and the University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. johnsonphi@chop.edu
authors.forename: Philip R
authors.initials: PR
authors.lastname: Johnson
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Schnepp
authors.forename: Jianchao
authors.initials: J
authors.lastname: Zhang
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Connell
authors.forename: Sean M
authors.initials: SM
authors.lastname: Greene
authors.forename: Eloisa
authors.initials: E
authors.lastname: Yuste
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Desrosiers
authors.forename: K Reed
authors.initials: KR
authors.lastname: Clark
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology* / Q000378:metabolism; D016860:CD4 Immunoadhesins / Q000276:immunology; D018014:Gene Transfer Techniques / Q000662:veterinary; D005822:Genetic Vectors / Q000276:immunology*; D000882:Haplorhini / Q000235:genetics / Q000276:immunology*; D007167:Immunotherapy / Q000379:methods / Q000662:veterinary; D008954:Models, Biological; D009500:Neutralization Tests; D018449:SAIDS Vaccines / Q000235:genetics / Q000627:therapeutic use*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D000914:Antibodies, Viral; D016860:CD4 Immunoadhesins; D018449:SAIDS Vaccines