Homologous vaccination has proven to be an effective tool to control and eradicate lumpy skin disease. However, their use has been met with some trepidation for diverse reasons, in some regions, and has resulted in the use of heterologous vaccines (sheeppox or goatpox-based). However, conflicting data (field and experimental) raises questions about their effectiveness. As comparative data under standardized conditions are lacking, this study aimed to evaluate four sheeppox-based and one goatpox-based vaccine using a standard vaccination/challenge protocol previously used to evaluate homologous LSDV vaccines. Although some minor differences were observed between the different sheeppox-based vaccines, none of them were able to completely protect the animals against a virulent LSDV challenge, as witnessed by the development of nodules, viremia and the detection of viral genomes in the different organs and tissues. In contrast, the goatpox-based vaccine provided complete protection (no nodules nor viremia) and induced an immunological profile (seroconversion and IFNγ response) similar to the homologous vaccines. Based upon the obtained data it can be concluded that none of the tested sheeppox-based vaccines are suitable for vaccination to prevent LSDV infection, at the dose used, while the goatpox-based vaccine, Caprivac, is. It should, however, be emphasized that this cannot be extrapolated to other goatpox-based vaccines without extensive validation.
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