A life-attenuated BLV deletant as a candidate vaccine to inhibit viral transmission in bovine herds

A life-attenuated BLV deletant as a candidate vaccine to inhibit viral transmission in bovine herds Sabrina M. Rodríguez1*†, Gerónimo Gutiérrez2*, Arnaud Florins3, Lucas Vagnoni2, Irene Alvarez2, Nicolas Gillet1, Karina Trono2‡, Luc Willems1,3‡ *‡S.M. Rodríguez / G. Gutiérrez and K.Trono / L. Willems contributed equally to this work. 1 Molecular and Cellular Epigenetics, Interdisciplinary Cluster for Applied Genoproteomics (GIGA), University of Liège (ULg), Liège (4100), Belgium. 2 Instituto de Virología, CICVyA, Instituto Nacional de Tecnología Agropecuaria, (1712), Castelar, Argentina. 3 Molecular and Cellular Biology, Gembloux Agro-Bio Tech, University of Liège (ULg), Gembloux (5030), Belgium †E-mail: sabrina.rodriguez@ulg.ac.be Bovine Leukemia Virus (BLV) is a major sanitary concern in many countries where the virus is widely disseminated among dairy herds with obvious economic impact. Different control strategies have been implemented worldwide to control BLV infection or eradicate the disease with diverse success. Eradication by culling is not economically sustainable in highly infected regions such as Argentina, US or Japan. Segregation of BLV-infected cattle is expensive due to duplication of facilities. Finally, several candidate vaccines based on recombinant viral proteins were unsuccessful to protect from challenge. Therefore, here we propose a novel strategy aimed to decrease seroprevalence based on the employ of a life-attenuated BLV provirus as a candidate vaccine. The rationale behind this strategy is the deletion of genes required to induce pathogenesis leaving those involved in infectivity, resulting in an attenuated deletant with impaired transmissibility. Preliminary experiments showed that the deletant provirus is infectious and elicits an efficient immune response in sheep (n=3) and in the natural host, bovines (n=9). Lack of spread to sentinels further supports the safety of the vaccine. Based on these promissory results, an ongoing validation program is being performed to evaluate the capacity of the candidate vaccine to protect from wild-type BLV infection in herd conditions (n=105). Infection will be routinely monitored and proviral loads will be determined. The efficiency of the immune response will be evaluated by titration of specific antibodies, cytotoxic lysis efficiency and cytokine profile. Viral expression ex vivo and provirus clonality will be also evaluated. This data will be instrumental for understanding the basic mechanisms undergoing during BLV infection and for elaborating a novel vaccine. We do believe this practical and cost-effective vaccination strategy is the sole economically viable in countries with high prevalence