title: Lack of protection following passive transfer of polyclonal highly functional low-dose non-neutralizing antibodies.
abstract: Recent immune correlates analysis from the RV144 vaccine trial has renewed interest in the role of non-neutralizing antibodies in mediating protection from infection. While neutralizing antibodies have proven difficult to induce through vaccination, extra-neutralizing antibodies, such as those that mediate antibody-dependent cellular cytotoxicity (ADCC), are associated with long-term control of infection. However, while several non-neutralizing monoclonal antibodies have been tested for their protective efficacy in vivo, no studies to date have tested the protective activity of naturally produced polyclonal antibodies from individuals harboring potent ADCC activity. Because ADCC-inducing antibodies are highly enriched in elite controllers (EC), we passively transferred highly functional non-neutralizing polyclonal antibodies, purified from an EC, to assess the potential impact of polyclonal non-neutralizing antibodies on a stringent SHIV-SF162P3 challenge in rhesus monkeys. Passive transfer of a low-dose of ADCC inducing antibodies did not protect from infection following SHIV-SF162P3 challenge. Passively administered antibody titers and gp120-specific, but not gp41-specific, ADCC and antibody induced phagocytosis (ADCP) were detected in the majority of the monkeys, but did not correlate with post infection viral control. Thus these data raise the possibility that gp120-specific ADCC activity alone may not be sufficient to control viremia post infection but that other specificities or Fc-effector profiles, alone or in combination, may have an impact on viral control and should be tested in future passive transfer experiments.
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Harvard University and Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Dugast
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Harvard University and Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chan
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Harvard University and Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Michelle
authors.initials: M
authors.lastname: Hoffner
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Harvard University and Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Anna
authors.initials: A
authors.lastname: Licht
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.
authors.forename: Joseph
authors.initials: J
authors.lastname: Nkolola
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.
authors.forename: Hualin
authors.initials: H
authors.lastname: Li
authors.affiliation: Military HIV Research Program, Henry Jackson Foundation, Rockville, Maryland, United States of America.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Streeck
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Harvard University and Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Todd J
authors.initials: TJ
authors.lastname: Suscovich
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Harvard University and Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Musie
authors.initials: M
authors.lastname: Ghebremichael
authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, United States of America.
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Ackerman
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Harvard University and Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.
authors.forename: Dan H
authors.initials: DH
authors.lastname: Barouch
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Harvard University and Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Galit
authors.initials: G
authors.lastname: Alter
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D000918:Antibody Specificity; D000920:Antibody-Dependent Cell Cytotoxicity; D004306:Dose-Response Relationship, Immunologic; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000276:immunology; D008253:Macaca mulatta; D008562:Membrane Glycoproteins / Q000276:immunology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; C069623:gp120 protein, Simian immunodeficiency virus