A life-attenuated BLV deletant as a candidate in bovine herds

GUTIERREZ GERONIMO; RODRIGUEZ SABRINA; FLORINS ARNAUD; VAGNONI LUCAS; ALVAREZ IRENE; GILLET NICOLAS; TRONO KARINA; WILLEMS LUC

RETROVIROLOGY

BIOMED CENTRAL LTD

Lugar: Londres; Año: 2011 vol. 8

1742-4690

There are different strategies to reduce BLV prevalence.Eradication by culling of infected animals is not economically sustainable in highly infected regions such asArgentina, US or Japan. Segregation of BLV-infectedcows is expensive due to duplication of facilities. Finally,several candidate vaccines based on recombinant viralproteins were unsuccessful to protect from challenge.Facing these problems, wepropose a novel strategybased on the use of a live-attenuated BLV provirus. Therationale behind this strategy relies on the deletion ofgenes required to induce pathogenesis leaving thoseinvolved in infectivity, resulting in an attenuated mutantwith impaired transmissibility.In a first set of experiments, we showed that themutant is infectious and elicits an efficient immuneresponse in sheep (n=3) and in cows (n=9). Lack ofspread to uninfected sentinels further supports thesafety of the vaccine. Based on these promising results,a validation program in herd (n=105) is ongoing to evaluate the capacity of the candidate vaccine to protectfrom wild-type BLV infection. The following experiments are carried out: quantification of the proviralloads, assessment of immune response efficiency (antibody titers, CTL response and cytokine profiling), measure of viral expression in vivo (qRT-PCR) and ex vivo(expression of Tax and p24gag) and determination ofprovirus clonality during infection.This data will be instrumental for understanding thebasic mechanisms undergoing during BLV infection andfor elaborating a novel vaccine.