A safe and effective vaccine against bovine leukemia virus

Abstract

Previous attempts to develop a vaccine against bovine leukemia virus (BLV) have not been successful because of inadequate or short-lived stimulation of all immunity components. In this study, we designed an approach based on an attenuated BLV provirus by deleting genes dispensable for infectivity but required for efficient replication. The ability of the vaccine to protect from natural BLV infection was investigated in the context of dairy productive conditions in an endemic region. The attenuated vaccine was tested in a farm in which the prevalence rose from 16.7% in young cattle at the beginning of the study to more than 90% in adult individuals. Sterilizing immunity was obtained in 28 out of 29 vaccinated heifers over a period of 48 months, demonstrating the effectiveness of the vaccine. As indicated by the antiviral antibody titers, the humoral response was slightly reduced compared to wild-type infection. After initial post-vaccination bursts, the proviral loads of the attenuated vaccine remained most frequently undetectable. During the first dairy cycle, proviral DNA was not detected by nested-PCR in milk samples from vaccinated cows. During the second dairy cycle, provirus was sporadically detected in milk of two vaccinated cows. Forty-two calves born from vaccinated cows were negative for proviral DNA but had antiviral antibodies in their peripheral blood. The attenuated strain was not transmitted to sentinels, further supporting the safety of the vaccine. Altogether, these data thus demonstrate that the vaccine against BLV is safe and effective in herd conditions characterized by a very high incidence. This cost-effective approach will thus decrease the prevalence of BLV without modification of production practices. After facing a series of challenges pertaining to effectiveness and biosafety, the vaccine is now available for further large-scale delivery. The different challenges and hurdles that were bypassed may be informative for the development of a vaccine against HTLV-1.

Genetic Variability of Bovine Leukemia Virus: Evidence of Dual Infection, Recombination and Quasi-Species

“…With regard to the present research, the issue of the occurrence of a superinfection or co-infection event is a critical question. Through the analogy of the model of cattle immunized with an attenuated virus and exposed to a circulating wild-type virus with high prevalence in the animal population, it can be assumed that it is rather impossible to infect an already infected cow through another BLV due to the strong host immune response [ 38 ]. Thus, superinfection seems illogical, as even cows immunized with the attenuated strain did not become infected with BLV wild-type from other cows kept with them for over 3 years [ 38 ].…”

“…Through the analogy of the model of cattle immunized with an attenuated virus and exposed to a circulating wild-type virus with high prevalence in the animal population, it can be assumed that it is rather impossible to infect an already infected cow through another BLV due to the strong host immune response [ 38 ]. Thus, superinfection seems illogical, as even cows immunized with the attenuated strain did not become infected with BLV wild-type from other cows kept with them for over 3 years [ 38 ]. Although the mechanism for the development of the dual infection, in our case, cannot be elucidated in detail, we suppose that it was possibly an accidental co-infection with dual pathogen genotypes.…”

The Global Epidemiology of Bovine Leukemia Virus: Current Trends and Future Implications

“…DNA vaccines containing the env and tax genes, controlled by cytomegalovirus or Srα promoters, demonstrated strong immune responses but were unable to prevent subsequent BLV infections [239,240]. Excitingly, an attenuated virus vaccine developed through gene deletion or mutation has been reported to effectively protect cattle from BLV infection [241]. However, the efficacy and biosafety of this vaccine require further validation.…”

Milk Transmission of Mammalian Retroviruses

“…The migration of these infected cells leads to tumors in the spleen and to a lesser extent in the liver, eye, heart, skin, lung, and lymph nodes [ 159 , 160 , 161 , 162 ]. Recently, a safe and effective vaccine against BLV based on an attenuated provirus has been developed, which may substitute the ‘test and eliminate’ and ‘test and segregate’ strategy [ 163 , 164 ]. Finally, it should be mentioned that there are controversial studies about a potential role of BLV in human breast cancer upon bovine-to-human transmission by milk or meat [ 165 , 166 , 167 , 168 ].…”