title: Dimeric 2G12 as a potent protection against HIV-1.
abstract: We previously showed that broadly neutralizing anti-HIV-1 antibody 2G12 (human IgG1) naturally forms dimers that are more potent than monomeric 2G12 in in vitro neutralization of various strains of HIV-1. In this study, we have investigated the protective effects of monomeric versus dimeric 2G12 against HIV-1 infection in vivo using a humanized mouse model. Our results showed that passively transferred, purified 2G12 dimer is more potent than 2G12 monomer at preventing CD4 T cell loss and suppressing the increase of viral load following HIV-1 infection of humanized mice. Using humanized mice bearing IgG "backpack" tumors that provided 2G12 antibodies continuously, we found that a sustained dimer concentration of 5-25 µg/ml during the course of infection provides effective protection against HIV-1. Importantly, 2G12 dimer at this concentration does not favor mutations of the HIV-1 envelope that would cause the virus to completely escape 2G12 neutralization. We have therefore identified dimeric 2G12 as a potent prophylactic reagent against HIV-1 in vivo, which could be used as part of an antibody cocktail to prevent HIV-1 infection.
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena, California, United States of America.
authors.forename: Xin M
authors.initials: XM
authors.lastname: Luo
authors.forename: Margarida Y Y
authors.initials: MY
authors.lastname: Lei
authors.forename: Rana A
authors.initials: RA
authors.lastname: Feidi
authors.forename: Anthony P
authors.initials: AP
authors.lastname: West
authors.forename: Alejandro Benjamin
authors.initials: AB
authors.lastname: Balazs
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Bjorkman
authors.forename: Lili
authors.initials: L
authors.lastname: Yang
authors.forename: David
authors.initials: D
authors.lastname: Baltimore
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology* / Q000627:therapeutic use; D000818:Animals; D015496:CD4-Positive T-Lymphocytes; D015483:HIV Antibodies / Q000276:immunology / Q000627:therapeutic use*; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G; D018655:Lymphocyte Count; D051379:Mice; D008822:Mice, Transgenic; D055503:Protein Multimerization; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D016915:AIDS Vaccines; D015483:HIV Antibodies; D007074:Immunoglobulin G