BLV: lessons on vaccine development

Abdala, Alejandro Ariel; Álvarez, Irene; Brossel, Hélène; Calvinho, Luis Fernando; Carignano, Hugo Adrián; Franco, Lautaro Nahuel; Gazon, Hélène; Gillissen, Christelle; Hamaïdia, Malik; Hoyos, Clotilde; Jacques, Jean-Rock; Joris, Thomas; Laval, Florent; Petersen, Marcos Iván; Porquet, Florent; Porta, Natalia Gabriela; Ruiz, Vanesa; Safari, Roghaiyeh; Archilla, Guillermo Alejandro Suarez; Trono, K.; Willems, Luc

doi:10.1186/s12977-019-0488-8

Cited by 19 publications

(13 citation statements)

References 44 publications

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“…This live-attenuated vaccine is infectious in cattle but replicates at reduced levels in cows and is able to efficiently stimulate the humoral and cellular immune response in cattle (84). However, risks as genetic drift, antigenic change or acquisition of mutations that increase pathogenicity, such as substituting by N230E of an N-linked envelope glycosylation site, must be considered significant concerns (18).…”

Section: Discussionmentioning

confidence: 99%

“…Recently, a new viral-attenuated vaccine platform based on a BLV provirus with multiple deletions in oncogenic genes (tax, G4, microRNAs) and genes responsible for infectivity or replication was reported (env and G3). This modified provirus is infectious in cattle but displays deficient levels of replication (18,19). This approach is auspicious, but several regulatory aspects must be solved before its massive use.…”

Section: Introductionmentioning

confidence: 99%

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Expression, Purification, and Characterization of Bovine Leukemia Virus-Like Particles Produced in Drosophila S2 Cells

et al. 2021

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Bovine leukemia virus (BLV) is an oncogenic deltaretrovirus that infects cattle worldwide. In Uruguay, it is estimated that more than 70% of dairy cattle are infected, causing serious economic losses due to decreased milk production, increased calving interval, and livestock losses due to lymphosarcoma. Several attempts to develop vaccine candidates that activate protective immune responses against BLV were performed, but up to date, there is no vaccine that ensures efficient protection and/or decreased viral transmission. The development and application of new vaccines that effectively control BLV infection represent a major challenge for countries with a high prevalence of infection. In this study, we generated two Drosophila melanogaster S2 stable cell lines capable of producing BLV virus-like particles (BLV-VLPs). One of them, BLV-VLP1, expressed both Gag and Env wild-type (Envwt) full-length proteins, whereas BLV-VLP2 contain Gag together with a mutant form of Env non-susceptible to proteolytic maturation by cellular furin type enzymes (EnvFm). We showed that Envwt is properly cleaved by cellular furin, whereas EnvFm is produced as a full-length gp72 precursor, which undergoes some partial cleavage. We observed that said mutation does not drastically affect its expression or its entry into the secretory pathway of S2 insect cells. In addition, it is expressed on the membrane and retains significant structural motifs when expressed in S2 insect cells. Morphology and size of purified BLV-VLPs were analyzed by transmission electron microscopy and dynamic light scattering, showing numerous non-aggregated and approximately spherical particles of variable diameter (70–200 nm) as previously reported for retroviral VLPs produced using different expression systems. Furthermore, we identified two N-glycosylation patterns rich in mannose in EnvFm protein displayed on VLP2. Our results suggest that the VLPs produced in Drosophila S2 cells could be a potential immunogen to be used in the development of BLV vaccines that might contribute, in conjunction with other control strategies, to reduce the transmission of the virus.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Expression, Purification, and Characterization of Bovine Leukemia Virus-Like Particles Produced in Drosophila S2 Cells

et al. 2021

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“…Despite trials of vaccines against BLV, there is no effective therapy or commercial vaccine yet available for the control of EBL, mainly because trials show only an incomplete or transient stimulation of the host immune response [11,225].…”

Section: Strategies For the Control Of Blv Infectionmentioning

confidence: 99%

Bovine Leukaemia Virus: Current Epidemiological Circumstance and Future Prospective

Marawan

Alouffi

Tokhy

et al. 2021

Viruses

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Bovine leukaemia virus (BLV) is a deltaretrovirus that is closely related to human T-cell leukaemia virus types 1 and 2 (HTLV-1 and -2). It causes enzootic bovine leukosis (EBL), which is the most important neoplastic disease in cattle. Most BLV-infected cattle are asymptomatic, which potentiates extremely high shedding rates of the virus in many cattle populations. Approximately 30% of them show persistent lymphocytosis that has various clinical outcomes; only a small proportion of animals (less than 5%) exhibit signs of EBL. BLV causes major economic losses in the cattle industry, especially in dairy farms. Direct costs are due to a decrease in animal productivity and in cow longevity; indirect costs are caused by restrictions that are placed on the import of animals and animal products from infected areas. Most European regions have implemented an efficient eradication programme, yet BLV prevalence remains high worldwide. Control of the disease is not feasible because there is no effective vaccine against it. Therefore, detection and early diagnosis of the disease are essential in order to diminish its spreading and the economic losses it causes. This review comprises an overview of bovine leukosis, which highlights the epidemiology of the disease, diagnostic tests that are used and effective control strategies.

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“…Sin embargo, debido a que el BLV es un retrovirus, el desarrollo de una vacuna eficaz no es una tarea fácil. Si bien, tanto los bovinos como los ovinos, son capaces de desarrollar una fuerte respuesta inmunitaria antiviral frente a la infección primaria por el BLV, las respuestas inmunitaria humoral e inmunitaria mediada por células son deficientes para la eliminación de células infectadas que portan el virus latente (Abdala et al, 2019).…”

Section: Vacunasunclassified

Leucosis bovina

Gutiérrez¹,

Lützelschwab²,

Barrios³

et al. 2020

Rev. investig. vet. Perú

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La leucosis bovina enzoótica, causada por el virus de la leucosis bovina (BLV), es la enfermedad tumoral más frecuente del bovino. Las razas bovinas de leche y de carne son susceptibles a la infección por BLV y al linfosarcoma; sin embargo la enfermedad es más prevalente en rodeos lecheros, principalmente debido a las prácticas de manejo. La patogenicidad del BLV en el bovino está asociada a la genética del animal. La mayoría de los bovinos infectados por el BLV son asintomáticos, por lo que la infección puede pasar desapercibida cuando los índices de infección son relativamente bajos. En ausencia de medidas de control, el virus se disemina lentamente entre los animales del rodeo. El BLV causa importantes pérdidas productivas, no sólo debido a la mortandad de animales con linfosarcoma, sino también por las restricciones al comercio de animales infectados y sus subproductos. Existen distintas alternativas para el control del BLV, adecuadas para distintas situaciones epidemiológicas. Hasta el momento no existe ningún tratamiento o vacuna eficaz para el control de este virus. Cuando la prevalencia de infección es baja, inferior al 10-15% de animales infectados, se recomienda identificar y eliminar la totalidad de los animales infectados. Esta alternativa no se adecúa a rodeos con altas prevalencias de infección, como ocurre con la mayoría de los rodeos lecheros en Argentina. La selección genética de animales resistentes a la diseminación del BLV surge como una estrategia natural para limitar la diseminación de este virus y, por ende, para el control del linfosarcoma asociado.

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BLV: lessons on vaccine development

Cited by 19 publications

References 44 publications

Expression, Purification, and Characterization of Bovine Leukemia Virus-Like Particles Produced in Drosophila S2 Cells

Expression, Purification, and Characterization of Bovine Leukemia Virus-Like Particles Produced in Drosophila S2 Cells

Bovine Leukaemia Virus: Current Epidemiological Circumstance and Future Prospective

Leucosis bovina

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