Cellular Targeting of Engineered Heterologous Antigens Is a Determinant Factor for Bovine Herpesvirus 4-Based Vaccine Vector Development

Donofrío, Gaetano; Franceschi, Valentina; Capocefalo, Antonio; Taddei, Simone; Sartori, Chiara; Bonomini, Sabrina; Cavirani, S.; Cabassi, Clotilde Silvia; Flammini, C. F.

doi:10.1128/cvi.00224-09

Cited by 23 publications

(33 citation statements)

References 27 publications

(28 reference statements)

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“…2E ). Therefore, the introduction of the CMV-gD cp gD 106 heterologous expression cassette into BoHV-4 genome TK locus does not confer detrimental effects as previously shown for other heterologous expression cassettes [17], [20], [21], [27].…”

Section: Resultssupporting

confidence: 58%

Clinical Protection of Goats against CpHV-1 Induced Genital Disease with a BoHV-4-Based Vector Expressing CpHV-1 gD

et al. 2013

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Caprine herpesvirus type 1 (CpHV-1) is an alphaherpesvirus causing genital disease leading to abortion in adult pregnant goats and a systemic disease with high morbility and mortality in kids. Further, Caprine herpesvirus 1 infection represents a valuable large animal model for human herpesvirus induced genital disease, exploitable for pathogenic studies, new vaccines and antiviral molecules testing. Here, the bovine herpesvirus 4 (BoHV-4) based vector derived from an apathogenic isolate of BoHV-4 and expressing the immunodominant CpHV-1 glycoprotein D (BoHV-4-A-gDcpgD106ΔTK) was constructed and its ability to protect goats against CpHV-1 induced genital disease evaluated. The subcutaneous route of recombinant BoHV-4 administration was first tested in vivo/ex vivo by in vivo image analysis and in vitro by goat skin primary cultures preparation and transduction. Next, an exploratory immunization and safety study in goats was performed with two recombinant BoHV4, BoHV-4-A-gDcpgD106ΔTK or BoHV-4-CMV-IgK-gE2gD-TM. In both cases no clinical signs were evident but a good titer of serum neutralizing antibodies was produced in all inoculated animals. When a challenge experiment was performed in a new group of animals using a highly pathogenic dose of CpHV-1, all the vaccinated goats with BoHV-4-A-gDcpgD106ΔTK were protected toward CpHV-1 induced genital disease respect to the unvaccinated control which showed typical vaginal lesions with a high grade of clinical score as well as a long lasting viral shedding. In summary, the data acquired in the present study validate BoHV-4-based vector as a safe and effective viral vector for goat vaccination against CpHV-1 induced genital disease and pave the way for further applications.

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Section: Resultssupporting

confidence: 58%

Clinical Protection of Goats against CpHV-1 Induced Genital Disease with a BoHV-4-Based Vector Expressing CpHV-1 gD

et al. 2013

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“…Due to the lack of a direct correlation between BoHV-4 infection and specific lesions or pathology, BoHV-4 is not considered a primary pathogen and its genome was cloned as bacterial artificial chromosome (BAC), in order to be exploited as a gene delivery vector for immunization purposes and oncolysis. BoHV-4-based vector delivering antigens have been employed to immunize mice [9], rats [11], rabbits [12], sheep [13], swine [14], cows (paper in preparation) and goats [15] without any associated clinical signs or pathology.…”

Section: Discussionmentioning

confidence: 99%

“…The 1967 bp amplicon for EBO digoxigenin-labeled probe was generated by PCR with Nhe I EBOGP sense (5′-ggggctagcccaccatgggcgtg-3′) and Sal I-EBOGP antisense (5′-ggggtcgacctggcgccagccggtccaccagtt 3′) primers, as previously described [12]. …”

Section: Methodsmentioning

confidence: 99%

“…Bovine herpesvirus 4 (BoHV-4)-is a relatively new viral vector derived from bovine gammaherpesvirus . Recombinant BoHV-4s cloned as bacterial artificial chromosome (BAC), delivering ORFs coding for immune-dominant antigens from different pathogens, were shown to successfully elicit a functional immune-response in mice [9, 10], rats [11], rabbits [12], sheep [13], swine [14] and goats [15]. In the present paper, a BoHV-4-based vector platform was generated exploiting a synthetic gene approach; a recombinant BoHV-4 delivering EBOV GP ORF expression cassette was constructed and goats were successfully immunized.…”

Section: Introductionmentioning

confidence: 99%

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BoHV-4-based vector delivering Ebola virus surface glycoprotein

et al. 2016

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BackgroundEbola virus (EBOV) is a Category A pathogen that is a member of Filoviridae family that causes hemorrhagic fever in humans and non-human primates. Unpredictable and devastating outbreaks of disease have recently occurred in Africa and current immunoprophylaxis and therapies are limited. The main limitation of working with pathogens like EBOV is the need for costly containment. To potentiate further and wider opportunity for EBOV prophylactics and therapies development, innovative approaches are necessary.MethodsIn the present study, an antigen delivery platform based on a recombinant bovine herpesvirus 4 (BoHV-4), delivering a synthetic EBOV glycoprotein (GP) gene sequence, BoHV-4-syEBOVgD106ΔTK, was generated.ResultsEBOV GP was abundantly expressed by BoHV-4-syEBOVgD106ΔTK transduced cells without decreasing viral replication. BoHV-4-syEBOVgD106ΔTK immunized goats produced high titers of anti-EBOV GP antibodies and conferred a long lasting (up to 6 months), detectable antibody response. Furthermore, no evidence of BoHV-4-syEBOVgD106ΔTK viremia and secondary localization was detected in any of the immunized animals.ConclusionsThe BoHV-4-based vector approach described here, represents: an alternative antigen delivery system for vaccination and a proof of principle study for anti-EBOV antibodies generation in goats for potential immunotherapy applications.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-1084-5) contains supplementary material, which is available to authorized users.

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“…Recientemente se han obtenido resultados satisfactorios en estudios en los que se utilizó una cepa apatógena de BoHV-4 como vector de péptidos inmunogénicos de otros agentes virales (virus de la diarrea viral bovina y herpesvirus bovino 1) 31 , lo cual confirma la potencialidad de su utilización como herramienta biológica.…”

Section: Antigenicidad Viral Y Respuesta Inmuneunclassified

Herpesvirus bovino 4 (BoHV-4): aspectos generales de su biología y situación en la República Argentina

Morán

Pérez

Odeón

et al. 2015

Revista Argentina de Microbiología

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Bovine herpesvirus 4 (BoHV-4) has been isolated from cattle with respiratory infections, vulvovaginitis, mastitis, abortions, endometritis and from apparently healthy animals throughout the world. Although it has not yet been established as causal agent of a specific disease entity, it is primarily associated with reproductive disorders of cattle. This virus can infect a wide range of species, either in vivo or in vitro. Two groups of prototype strains were originated from the first isolates: the DN599-type strains (American group) and the Movar-type strains (European group). In Argentina, BoHV-4 was isolated and characterized in 2007 from vaginal discharge samples taken from cows that had aborted. So far, more than 40 isolates, mainly associated with aborting bovine females have been registered in our country.

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Cellular Targeting of Engineered Heterologous Antigens Is a Determinant Factor for Bovine Herpesvirus 4-Based Vaccine Vector Development

Cited by 23 publications

References 27 publications

Clinical Protection of Goats against CpHV-1 Induced Genital Disease with a BoHV-4-Based Vector Expressing CpHV-1 gD

Clinical Protection of Goats against CpHV-1 Induced Genital Disease with a BoHV-4-Based Vector Expressing CpHV-1 gD

BoHV-4-based vector delivering Ebola virus surface glycoprotein

Herpesvirus bovino 4 (BoHV-4): aspectos generales de su biología y situación en la República Argentina

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