Antibody-mediated protection against SHIV challenge includes systemic clearance of distal virus

Jinyan Liu; Khader Ghneim; Devin Sok; William J Bosche; Yuan Li; Elizabeth Chipriano; Brian Berkemeier; Kelli Oswald; Erica Borducchi; Crystal Cabral; Lauren Peter; Amanda Brinkman; Mayuri Shetty; Jessica Jimenez; Jade Mondesir; Benjamin Lee; Patricia Giglio; Abishek Chandrashekar; Peter Abbink; Arnaud Colantonio; Courtney Gittens; Chantelle Baker; Wendeline Wagner; Mark G Lewis; Wenjun Li; Rafick-Pierre Sekaly; Jeffrey D Lifson; Dennis R Burton; Dan H Barouch

doi:10.1126/science.aag0491

Antibody-mediated protection against SHIV challenge includes systemic clearance of distal virus

Science. 2016 Sep 2;353(6303):1045-1049. doi: 10.1126/science.aag0491. Epub 2016 Aug 18.

Authors

Jinyan Liu¹, Khader Ghneim², Devin Sok³, William J Bosche⁴, Yuan Li⁴, Elizabeth Chipriano⁴, Brian Berkemeier⁴, Kelli Oswald⁴, Erica Borducchi¹, Crystal Cabral¹, Lauren Peter¹, Amanda Brinkman¹, Mayuri Shetty¹, Jessica Jimenez¹, Jade Mondesir¹, Benjamin Lee¹, Patricia Giglio¹, Abishek Chandrashekar¹, Peter Abbink¹, Arnaud Colantonio⁵, Courtney Gittens⁶, Chantelle Baker⁶, Wendeline Wagner⁶, Mark G Lewis⁶, Wenjun Li⁷, Rafick-Pierre Sekaly², Jeffrey D Lifson⁴, Dennis R Burton⁸, Dan H Barouch⁹

Affiliations

¹ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
² Case Western Reserve University, Cleveland, OH 44106, USA.
³ The Scripps Research Institute, La Jolla, CA 92037, USA.
⁴ AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory, Frederick, MD 21702, USA.
⁵ Harvard Medical School, Boston, MA 02115, USA.
⁶ Bioqual, Rockville, MD 20852, USA.
⁷ University of Massachusetts Medical School, Worcester, MA 01655, USA.
⁸ 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.
⁹ 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.

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.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Adoptive Transfer
Animals
Antibodies, Neutralizing / administration & dosage*
Antibodies, Neutralizing / immunology
DNA, Viral / analysis
Female
HIV Antibodies / administration & dosage*
HIV Antibodies / immunology
HIV-1 / immunology*
Immunity, Innate / genetics
Immunity, Innate / immunology
Macaca mulatta
RNA, Viral / analysis
Simian Acquired Immunodeficiency Syndrome / prevention & control*
Simian Immunodeficiency Virus / immunology*
Transcriptome
Vagina / virology

Substances

Antibodies, Neutralizing
DNA, Viral
HIV Antibodies
RNA, Viral

Abstract

Publication types

MeSH terms

Substances

Grants and funding