Induction of Antihuman C–C Chemokine Receptor Type 5 Antibodies by a Bovine Herpesvirus Type-4 Based Vector
Bovine herpesvirus 4 (BoHV-4) is a promising vector for the delivery and intracellular expression of recombinant antigens and can thus be considered as a new prototype vaccine formulation system. An interesting, and actively pursued, antigen in the context of human immunodeficiency virus (HIV) infec...
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doaj-b4070a21624548d288ecd11298d433c32020-11-24T21:25:55ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-10-01810.3389/fimmu.2017.01402302113Induction of Antihuman C–C Chemokine Receptor Type 5 Antibodies by a Bovine Herpesvirus Type-4 Based VectorAndrea Elizabeth Verna0Valentina Franceschi1Giulia Tebaldi2Francesca Macchi3Valentina Menozzi4Claudia Pastori5Lucia Lopalco6Simone Ottonello7Sandro Cavirani8Gaetano Donofrio9Department of Medical Veterinary Science, University of Parma, Parma, ItalyDepartment of Medical Veterinary Science, University of Parma, Parma, ItalyDepartment of Medical Veterinary Science, University of Parma, Parma, ItalyDepartment of Medical Veterinary Science, University of Parma, Parma, ItalyDepartment of Medical Veterinary Science, University of Parma, Parma, ItalyDivision of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milan, ItalyDivision of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milan, ItalyBiochemistry and Molecular Biology Unit, Laboratory of Functional Genomics and Protein Engineering, Department of Life Sciences, University of Parma, Parma, ItalyDepartment of Medical Veterinary Science, University of Parma, Parma, ItalyDepartment of Medical Veterinary Science, University of Parma, Parma, ItalyBovine herpesvirus 4 (BoHV-4) is a promising vector for the delivery and intracellular expression of recombinant antigens and can thus be considered as a new prototype vaccine formulation system. An interesting, and actively pursued, antigen in the context of human immunodeficiency virus (HIV) infection prophylaxis (and therapy) is the C–C chemokine receptor type 5 (CCR5) co-receptor, whose blockage by specific antibodies has been shown to inhibit both viral entry and cell-to-cell transmission of the virus. Building on our previous work on the BoHV-4 vector system, we have engineered and tested a replication-competent derivative of BoHV-4 (BoHV-4-CMV-hCCR5ΔTK) bearing a human CCR5 (hCCR5) expression cassette. We show here that CCR5 is indeed expressed at high levels in multiple types of BoHV-4-CMV-hCCR5ΔTK-infected cells. More importantly, two intravenous inoculations of CCR5-expressing BoHV-4 virions into rabbits led to the production of anti-CCR5 antibodies capable of reacting with the CCR5 receptor exposed on the surface of HEK293T cells through specific recognition of the amino-terminal region (aa 14–34) of the protein. Given the growing interest for anti-CCR5 immunization as an HIV control strategy and the many advantages of virus-based immunogen formulations (especially for poorly immunogenic or self-antigens), the results reported in this study provide preliminary validation of BoHV-4 as a safe viral vector suitable for CCR5 vaccination.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01402/fullbovine herpesvirus 4gene delivery vectorhuman CCR5recombinant virusantihuman CCR5 antibodies |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Andrea Elizabeth Verna Valentina Franceschi Giulia Tebaldi Francesca Macchi Valentina Menozzi Claudia Pastori Lucia Lopalco Simone Ottonello Sandro Cavirani Gaetano Donofrio |
spellingShingle |
Andrea Elizabeth Verna Valentina Franceschi Giulia Tebaldi Francesca Macchi Valentina Menozzi Claudia Pastori Lucia Lopalco Simone Ottonello Sandro Cavirani Gaetano Donofrio Induction of Antihuman C–C Chemokine Receptor Type 5 Antibodies by a Bovine Herpesvirus Type-4 Based Vector Frontiers in Immunology bovine herpesvirus 4 gene delivery vector human CCR5 recombinant virus antihuman CCR5 antibodies |
author_facet |
Andrea Elizabeth Verna Valentina Franceschi Giulia Tebaldi Francesca Macchi Valentina Menozzi Claudia Pastori Lucia Lopalco Simone Ottonello Sandro Cavirani Gaetano Donofrio |
author_sort |
Andrea Elizabeth Verna |
title |
Induction of Antihuman C–C Chemokine Receptor Type 5 Antibodies by a Bovine Herpesvirus Type-4 Based Vector |
title_short |
Induction of Antihuman C–C Chemokine Receptor Type 5 Antibodies by a Bovine Herpesvirus Type-4 Based Vector |
title_full |
Induction of Antihuman C–C Chemokine Receptor Type 5 Antibodies by a Bovine Herpesvirus Type-4 Based Vector |
title_fullStr |
Induction of Antihuman C–C Chemokine Receptor Type 5 Antibodies by a Bovine Herpesvirus Type-4 Based Vector |
title_full_unstemmed |
Induction of Antihuman C–C Chemokine Receptor Type 5 Antibodies by a Bovine Herpesvirus Type-4 Based Vector |
title_sort |
induction of antihuman c–c chemokine receptor type 5 antibodies by a bovine herpesvirus type-4 based vector |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2017-10-01 |
description |
Bovine herpesvirus 4 (BoHV-4) is a promising vector for the delivery and intracellular expression of recombinant antigens and can thus be considered as a new prototype vaccine formulation system. An interesting, and actively pursued, antigen in the context of human immunodeficiency virus (HIV) infection prophylaxis (and therapy) is the C–C chemokine receptor type 5 (CCR5) co-receptor, whose blockage by specific antibodies has been shown to inhibit both viral entry and cell-to-cell transmission of the virus. Building on our previous work on the BoHV-4 vector system, we have engineered and tested a replication-competent derivative of BoHV-4 (BoHV-4-CMV-hCCR5ΔTK) bearing a human CCR5 (hCCR5) expression cassette. We show here that CCR5 is indeed expressed at high levels in multiple types of BoHV-4-CMV-hCCR5ΔTK-infected cells. More importantly, two intravenous inoculations of CCR5-expressing BoHV-4 virions into rabbits led to the production of anti-CCR5 antibodies capable of reacting with the CCR5 receptor exposed on the surface of HEK293T cells through specific recognition of the amino-terminal region (aa 14–34) of the protein. Given the growing interest for anti-CCR5 immunization as an HIV control strategy and the many advantages of virus-based immunogen formulations (especially for poorly immunogenic or self-antigens), the results reported in this study provide preliminary validation of BoHV-4 as a safe viral vector suitable for CCR5 vaccination. |
topic |
bovine herpesvirus 4 gene delivery vector human CCR5 recombinant virus antihuman CCR5 antibodies |
url |
http://journal.frontiersin.org/article/10.3389/fimmu.2017.01402/full |
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