title: Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys.
abstract: Human immunodeficiency virus type 1 (HIV-1)-specific monoclonal antibodies with extraordinary potency and breadth have recently been described. In humanized mice, combinations of monoclonal antibodies have been shown to suppress viraemia, but the therapeutic potential of these monoclonal antibodies has not yet been evaluated in primates with an intact immune system. Here we show that administration of a cocktail of HIV-1-specific monoclonal antibodies, as well as the single glycan-dependent monoclonal antibody PGT121, resulted in a rapid and precipitous decline of plasma viraemia to undetectable levels in rhesus monkeys chronically infected with the pathogenic simian-human immunodeficiency virus SHIV-SF162P3. A single monoclonal antibody infusion afforded up to a 3.1 log decline of plasma viral RNA in 7 days and also reduced proviral DNA in peripheral blood, gastrointestinal mucosa and lymph nodes without the development of viral resistance. Moreover, after monoclonal antibody administration, host Gag-specific T-lymphocyte responses showed improved functionality. Virus rebounded in most animals after a median of 56 days when serum monoclonal antibody titres had declined to undetectable levels, although, notably, a subset of animals maintained long-term virological control in the absence of further monoclonal antibody infusions. These data demonstrate a profound therapeutic effect of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys as well as an impact on host immune responses. Our findings strongly encourage the investigation of monoclonal antibody therapy for HIV-1 in humans.
authors.affiliation: 1] Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA [2] Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts 02139, USA.
authors.forename: Dan H
authors.initials: DH
authors.lastname: Barouch
authors.forename: James B
authors.initials: JB
authors.lastname: Whitney
authors.forename: Brian
authors.initials: B
authors.lastname: Moldt
authors.forename: Florian
authors.initials: F
authors.lastname: Klein
authors.forename: Thiago Y
authors.initials: TY
authors.lastname: Oliveira
authors.forename: Jinyan
authors.initials: J
authors.lastname: Liu
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Stephenson
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Chang
authors.forename: Karthik
authors.initials: K
authors.lastname: Shekhar
authors.forename: Sanjana
authors.initials: S
authors.lastname: Gupta
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Nkolola
authors.forename: Michael S
authors.initials: MS
authors.lastname: Seaman
authors.forename: Kaitlin M
authors.initials: KM
authors.lastname: Smith
authors.forename: Erica N
authors.initials: EN
authors.lastname: Borducchi
authors.forename: Crystal
authors.initials: C
authors.lastname: Cabral
authors.forename: Jeffrey Y
authors.initials: JY
authors.lastname: Smith
authors.forename: Stephen
authors.initials: S
authors.lastname: Blackmore
authors.forename: Srisowmya
authors.initials: S
authors.lastname: Sanisetty
authors.forename: James R
authors.initials: JR
authors.lastname: Perry
authors.forename: Matthew
authors.initials: M
authors.lastname: Beck
authors.forename: Mark G
authors.initials: MG
authors.lastname: Lewis
authors.forename: William
authors.initials: W
authors.lastname: Rinaldi
authors.forename: Arup K
authors.initials: AK
authors.lastname: Chakraborty
authors.forename: Pascal
authors.initials: P
authors.lastname: Poignard
authors.forename: Michel C
authors.initials: MC
authors.lastname: Nussenzweig
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D057134:Antibodies, Neutralizing / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D015483:HIV Antibodies / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000628:therapy*; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology; D014766:Viremia / Q000628:therapy
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D004279:DNA, Viral; D015483:HIV Antibodies