Inclusion of CD80 in HSV targets the recombinant virus to PD-L1 on DCs and allows productive infection and robust immune responses.
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.
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.
Kevin R
KR
Mott
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.
Sariah J
SJ
Allen
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.
Mandana
M
Zandian
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
Omid
O
Akbari
Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States of America.
Pedram
P
Hamrah
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
Hadi
H
Maazi
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.
Steven L
SL
Wechsler
Department of Pathology, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
Arlene H
AH
Sharpe
Department of Medical Oncology, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America.
Gordon J
GJ
Freeman
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.
Homayon
H
Ghiasi
D000276:Adjuvants, Immunologic / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics* / Q000378:metabolism; D060890:B7-H1 Antigen / Q000378:metabolism; D015139:Blotting, Southern; D017931:DNA Primers / Q000235:genetics; D003713:Dendritic Cells / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005818:Genetic Engineering; D006561:Herpes Simplex / Q000235:genetics / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics; D011817:Rabbits; D060888:Real-Time Polymerase Chain Reaction; D011995:Recombination, Genetic / Q000235:genetics*; D014765:Viral Vaccines / Q000235:genetics*
D000276:Adjuvants, Immunologic; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D017931:DNA Primers; D035683:MicroRNAs; D014765:Viral Vaccines; C477253:latency associated transcript, herpes simplex virus-1