title: Early antibody therapy can induce long-lasting immunity to SHIV.
abstract: Highly potent and broadly neutralizing anti-HIV-1 antibodies (bNAbs) have been used to prevent and treat lentivirus infections in humanized mice, macaques, and humans. In immunotherapy experiments, administration of bNAbs to chronically infected animals transiently suppresses virus replication, which invariably returns to pre-treatment levels and results in progression to clinical disease. Here we show that early administration of bNAbs in a macaque simian/human immunodeficiency virus (SHIV) model is associated with very low levels of persistent viraemia, which leads to the establishment of T-cell immunity and resultant long-term infection control. Animals challenged with SHIVAD8-EOby mucosal or intravenous routes received a single 2-week course of two potent passively transferred bNAbs (3BNC117 and 10-1074 (refs 13, 14)). Viraemia remained undetectable for 56-177 days, depending on bNAb half-life in vivo. Moreover, in the 13 treated monkeys, plasma virus loads subsequently declined to undetectable levels in 6 controller macaques. Four additional animals maintained their counts of T cells carrying the CD4 antigen (CD4+) and very low levels of viraemia persisted for over 2 years. The frequency of cells carrying replication-competent virus was less than 1 per 106circulating CD4+T cells in the six controller macaques. Infusion of a T-cell-depleting anti-CD8β monoclonal antibody to the controller animals led to a specific decline in levels of CD8+T cells and the rapid reappearance of plasma viraemia. In contrast, macaques treated for 15 weeks with combination anti-retroviral therapy, beginning on day 3 after infection, experienced sustained rebound plasma viraemia when treatment was interrupted. Our results show that passive immunotherapy during acute SHIV infection differs from combination anti-retroviral therapy in that it facilitates the emergence of potent CD8+T-cell immunity able to durably suppress virus replication.
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Nishimura
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Gautam
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Tae-Wook
authors.initials: TW
authors.lastname: Chun
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Reza
authors.initials: R
authors.lastname: Sadjadpour
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892 USA.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Foulds
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Masashi
authors.initials: M
authors.lastname: Shingai
authors.affiliation: Institute of Virology, University of Cologne, 50931 Cologne, Germany.|Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Klein
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Gazumyan
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.
authors.forename: Jovana
authors.initials: J
authors.lastname: Golijanin
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892 USA.
authors.forename: Mitzi
authors.initials: M
authors.lastname: Donaldson
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Olivia K
authors.initials: OK
authors.lastname: Donau
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Plishka
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Alicia
authors.initials: A
authors.lastname: Buckler-White
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Seaman
authors.affiliation: AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892 USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Koup
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Fauci
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.|Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10065, USA.
authors.forename: Michel C
authors.initials: MC
authors.lastname: Nussenzweig
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Malcolm A
authors.initials: MA
authors.lastname: Martin
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use; D057134:Antibodies, Neutralizing / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D005260:Female; D006678:HIV / Q000187:drug effects / Q000276:immunology* / Q000302:isolation & purification; D015483:HIV Antibodies / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy* / Q000821:virology; D006207:Half-Life; D007116:Immunization, Passive; D008253:Macaca mulatta; D008297:Male; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology* / Q000628:therapy* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000187:drug effects / Q000276:immunology* / Q000302:isolation & purification; D019562:Viral Load / Q000187:drug effects / Q000276:immunology; D014766:Viremia / Q000276:immunology / Q000628:therapy; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology
chemical_list: D019380:Anti-HIV Agents; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies