2. Academic Validation
  3. Inclusion of CD80 in HSV targets the recombinant virus to PD-L1 on DCs and allows productive infection and robust immune responses

Inclusion of CD80 in HSV targets the recombinant virus to PD-L1 on DCs and allows productive infection and robust immune responses

  • PLoS One. 2014 Jan 27;9(1):e87617. doi: 10.1371/journal.pone.0087617.
Kevin R Mott 1,  Sariah J Allen 1,  Mandana Zandian 1,  Omid Akbari 2,  Pedram Hamrah 3,  Hadi Maazi 2,  Steven L Wechsler 4,  Arlene H Sharpe 5,  Gordon J Freeman 6,  Homayon Ghiasi 1
Affiliations

Affiliations

  • 1 Center for Neurobiology and Vaccine Development, Ophthalmology Research, Department of Surgery, Cedars-Sinai Burns & Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
  • 2 Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
  • 3 Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States of America.
  • 4 Gavin Herbert Eye Institute, the Department of Ophthalmology, the Department of Microbiology and Molecular Genetics, and the Center for Virus Research, University of California Irvine, School of Medicine, Irvine, California, United States of America.
  • 5 Department of Pathology, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
  • 6 Department of Medical Oncology, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America.
PMID: 24475315 DOI: 10.1371/journal.pone.0087617
Abstract

CD80 plays a critical role in stimulation of T cells and subsequent control of Infection. To investigate the effect of CD80 on HSV-1 Infection, we constructed a recombinant HSV-1 virus that expresses two copies of the CD80 gene in place of the latency associated transcript (LAT). This mutant virus (HSV-CD80) expressed high levels of CD80 and had similar virus replication kinetics as control viruses in rabbit skin cells. In contrast to parental virus, this CD80 expressing recombinant virus replicated efficiently in immature dendritic cells (DCs). Additionally, the susceptibility of immature DCs to HSV-CD80 Infection was mediated by CD80 binding to PD-L1 on DCs. This interaction also contributed to a significant increase in T cell activation. Taken together, these results suggest that inclusion of CD80 as a vaccine Adjuvant may promote increased vaccine efficacy by enhancing the immune response directly and also indirectly by targeting to DC.

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