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Science. 2016 Sep 2;353(6303):1045-1049. Epub 2016 Aug 18.

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

Author information

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.

PMID:
27540005
PMCID:
PMC5237379
DOI:
10.1126/science.aag0491
[Indexed for MEDLINE]
Free PMC Article

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