title: Broadly Neutralizing Human Immunodeficiency Virus Type 1 Antibody Gene Transfer Protects Nonhuman Primates from Mucosal Simian-Human Immunodeficiency Virus Infection.
abstract: Broadly neutralizing antibodies (bnAbs) can prevent lentiviral infection in nonhuman primates and may slow the spread of human immunodeficiency virus type 1 (HIV-1). Although protection by passive transfer of human bnAbs has been demonstrated in monkeys, durable expression is essential for its broader use in humans. Gene-based expression of bnAbs provides a potential solution to this problem, although immune responses to the viral vector or to the antibody may limit its durability and efficacy. Here, we delivered an adeno-associated viral vector encoding a simianized form of a CD4bs bnAb, VRC07, and evaluated its immunogenicity and protective efficacy. The expressed antibody circulated in macaques for 16 weeks at levels up to 66 g/ml, although immune suppression with cyclosporine (CsA) was needed to sustain expression. Gene-delivered simian VRC07 protected against simian-human immunodeficiency virus (SHIV) infection in monkeys 5.5 weeks after treatment. Gene transfer of an anti-HIV antibody can therefore protect against infection by viruses that cause AIDS in primates when the host immune responses are controlled.
authors.forename: Kevin O
authors.initials: KO
authors.lastname: Saunders
authors.forename: Lingshu
authors.initials: L
authors.lastname: Wang
authors.forename: M Gordon
authors.initials: MG
authors.lastname: Joyce
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Yang
authors.forename: Alejandro B
authors.initials: AB
authors.lastname: Balazs
authors.forename: Cheng
authors.initials: C
authors.lastname: Cheng
authors.forename: Sung-Youl
authors.initials: SY
authors.lastname: Ko
authors.forename: Wing-Pui
authors.initials: WP
authors.lastname: Kong
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Rudicell
authors.forename: Ivelin S
authors.initials: IS
authors.lastname: Georgiev
authors.forename: Lijie
authors.initials: L
authors.lastname: Duan
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Foulds
authors.forename: Mitzi
authors.initials: M
authors.lastname: Donaldson
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Schmidt
authors.forename: John-Paul
authors.initials: JP
authors.lastname: Todd
authors.forename: David
authors.initials: D
authors.lastname: Baltimore
authors.forename: Mario
authors.initials: M
authors.lastname: Roederer
authors.forename: Ashley T
authors.initials: AT
authors.lastname: Haase
authors.forename: Peter D
authors.initials: PD
authors.lastname: Kwong
authors.forename: Srinivas S
authors.initials: SS
authors.lastname: Rao
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Nabel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D057134:Antibodies, Neutralizing / Q000235:genetics / Q000276:immunology*; D016572:Cyclosporine / Q000494:pharmacology; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics; D015483:HIV Antibodies / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008253:Macaca mulatta; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D057134:Antibodies, Neutralizing; D017931:DNA Primers; D015483:HIV Antibodies; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D016572:Cyclosporine