title: Adenovirus-Vectored Broadly Neutralizing Antibodies Directed Against gp120 Prevent Human Immunodeficiency Virus Type 1 Acquisition in Humanized Mice.
abstract: Despite nearly three decades of research, a safe and effective vaccine against human immunodeficiency virus type 1 (HIV-1) has yet to be achieved. More recently, the discovery of highly potent anti-gp160 broadly neutralizing antibodies (bNAbs) has garnered renewed interest in using antibody-based prophylactic and therapeutic approaches. Here, we encoded bNAbs in first-generation adenoviral (ADV) vectors, which have the distinctive features of a large coding capacity and ease of propagation. A single intramuscular injection of ADV-vectorized bNAbs in humanized mice generated high serum levels of bNAbs that provided protection against multiple repeated challenges with a high dose of HIV-1, prevented depletion of peripheral CD4(+) T cells, and reduced plasma viral loads to below detection limits. Our results suggest that ADV vectors may be a viable option for the prophylactic and perhaps therapeutic use of bNAbs in humans.
authors.affiliation: Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine , New Haven, Connecticut.
authors.forename: Shan
authors.initials: S
authors.lastname: Liu
authors.affiliation: Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine , New Haven, Connecticut.
authors.forename: Andrew
authors.initials: A
authors.lastname: Jackson
authors.affiliation: Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine , New Haven, Connecticut.
authors.forename: Jagadish
authors.initials: J
authors.lastname: Beloor
authors.affiliation: Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine , New Haven, Connecticut.
authors.forename: Priti
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine , New Haven, Connecticut.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Sutton
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000235:genetics*; D005822:Genetic Vectors; D057809:HEK293 Cells; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014611:Vaccination
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015699:HIV Envelope Protein gp120; C514793:gp120 protein, Human immunodeficiency virus 1