title: Antibody-mediated protection against SHIV challenge includes systemic clearance of distal virus.
abstract: HIV-1-specific broadly neutralizing antibodies (bNAbs) can protect rhesus monkeys against simian-human immunodeficiency virus (SHIV) challenge. However, the site of antibody interception of virus and the mechanism of antibody-mediated protection remain unclear. We administered a fully protective dose of the bNAb PGT121 to rhesus monkeys and challenged them intravaginally with SHIV-SF162P3. In PGT121-treated animals, we detected low levels of viral RNA and viral DNA in distal tissues for seven days following challenge. Viral RNA-positive tissues showed transcriptomic changes indicative of innate immune activation, and cells from these tissues initiated infection after adoptive transfer into naïve hosts. These data demonstrate that bNAb-mediated protection against a mucosal virus challenge can involve clearance of infectious virus in distal tissues.
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Jinyan
authors.initials: J
authors.lastname: Liu
authors.affiliation: Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Khader
authors.initials: K
authors.lastname: Ghneim
authors.affiliation: The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Devin
authors.initials: D
authors.lastname: Sok
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory, Frederick, MD 21702, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Bosche
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory, Frederick, MD 21702, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory, Frederick, MD 21702, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Chipriano
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory, Frederick, MD 21702, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Berkemeier
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory, Frederick, MD 21702, USA.
authors.forename: Kelli
authors.initials: K
authors.lastname: Oswald
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Erica
authors.initials: E
authors.lastname: Borducchi
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Crystal
authors.initials: C
authors.lastname: Cabral
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Peter
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Brinkman
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Mayuri
authors.initials: M
authors.lastname: Shetty
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Jimenez
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Jade
authors.initials: J
authors.lastname: Mondesir
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lee
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Giglio
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Abishek
authors.initials: A
authors.lastname: Chandrashekar
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Abbink
authors.affiliation: Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Colantonio
authors.affiliation: Bioqual, Rockville, MD 20852, USA.
authors.forename: Courtney
authors.initials: C
authors.lastname: Gittens
authors.affiliation: Bioqual, Rockville, MD 20852, USA.
authors.forename: Chantelle
authors.initials: C
authors.lastname: Baker
authors.affiliation: Bioqual, Rockville, MD 20852, USA.
authors.forename: Wendeline
authors.initials: W
authors.lastname: Wagner
authors.affiliation: Bioqual, Rockville, MD 20852, USA.
authors.forename: Mark G
authors.initials: MG
authors.lastname: Lewis
authors.affiliation: University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Li
authors.affiliation: Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Rafick-Pierre
authors.initials: RP
authors.lastname: Sekaly
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory, Frederick, MD 21702, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.affiliation: The Scripps Research Institute, La Jolla, CA 92037, USA. Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge, MA 02139, USA.
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge, MA 02139, USA. dbarouch@bidmc.harvard.edu.
authors.forename: Dan H
authors.initials: DH
authors.lastname: Barouch
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D057134:Antibodies, Neutralizing / Q000008:administration & dosage* / Q000276:immunology; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D015483:HIV Antibodies / Q000008:administration & dosage* / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D008253:Macaca mulatta; D012367:RNA, Viral / Q000032:analysis; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D059467:Transcriptome; D014621:Vagina / Q000821:virology
chemical_list: D057134:Antibodies, Neutralizing; D004279:DNA, Viral; D015483:HIV Antibodies; D012367:RNA, Viral