The geographical distribution of lumpy skin disease (LSD), an economically important cattle disease caused by a capripoxvirus, has reached an unprecedented extent. Vaccination is the only way to prevent the spread of the infection in endemic and newly affected regions. Yet, in the event of an outbreak, selection of the best vaccine is a major challenge for veterinary authorities and farmers. Decision makers need sound scientific information to support their decisions and subsequent actions. The available vaccine products vary in terms of quality, efficacy, safety, side effects, and price. The pros and cons of different types of live attenuated and inactivated vaccines, vaccination strategies, and associated risks are discussed. Seroconversion, which typically follows vaccination, places specific demands on the tools and methods used to evaluate the effectiveness of the LSD vaccination campaigns in the field. We aimed to give a comprehensive update on available vaccines and vaccination against LSD, to better prepare affected and at-risk countries to control LSD and ensure the safe trade of cattle.

Lumpy skin disease (LSD) is a devastating disease of cattle characterized by fever, nodules on the skin, lymphadenopathy and milk drop. Several haematophagous arthropod species like dipterans and ticks are suspected to play a role in the transmission of LSDV. Few conclusive data are however available on the importance of biting flies and horseflies as potential vectors in LSDV transmission. Therefore an in vivo transmission study was carried out to investigate possible LSDV transmission by Stomoxys calcitrans biting flies and Haematopota spp. horseflies from experimentally infected viraemic donor bulls to acceptor bulls. LSDV transmission by Stomoxys calcitrans was evidenced in 3 independent experiments, LSDV transmission by Haematopota spp. was shown in one experiment. Evidence of LSD was supported by induction of nodules and virus detection in the blood of acceptor animals. Our results are supportive for a mechanical transmission of the virus by these vectors.

Foot and mouth disease (FMD) is a highly contagious viral disease with high economic impact, representing a major threat for cloven-hooved mammals worldwide. Vaccines based on adjuvanted inactivated virus (iFMDV) induce effective protective immunity implicating antibody (Ab) responses. To reduce the biosafety constraints of the manufacturing process, a non-replicative human adenovirus type 5 vector encoding FMDV antigens (Ad5-FMDV) has been developed. Here we compared the immunogenicity of iFMDV and Ad5-FMDV with and without the ISA206VG emulsion-type adjuvant in sheep. Contrasted Ab responses were obtained: iFMDV induced the highest Ab levels, Ad5-FMDV the lowest ones, and ISA206VG increased the Ad5-FMDV-induced Ab responses to protective levels. Each vaccine generated heterogeneous Ab responses, with high and low responders, the latter being considered as obstacles to vaccine effectiveness. A transcriptomic study on total blood responses at 24 h post-vaccination revealed several blood gene module activities correlating with long-term Ab responses. Downmodulation of T cell modules’ activities correlated with high responses to iFMDV and to Ad5-FMDV+ISA206VG vaccines as also found in other systems vaccinology studies in humans and sheep. The impact of cell cycle activity depended on the vaccine types, as it positively correlated with higher responses to iFMDV but negatively to non-adjuvanted Ad5-FMDV. Finally an elevated B cell activity at 24 h correlated with high Ab responses to the Ad5-FMDV+ISA206VG vaccine. This study provides insights into the early mechanisms driving the Ab response induced by different vaccine regimens including Ad5 vectors and points to T cell modules as early biomarker candidates of different vaccine-type efficacy across species.

Lumpy skin disease is a high-consequence disease in cattle caused by infection with the poxvirus lumpy skin disease virus (LSDV). The virus is endemic in most countries in Africa and an emerging threat to cattle populations in Europe and Asia. As LSDV spreads into new regions, it is important that signs of disease are recognized promptly by animal caregivers. This study describes the gross, microscopic, and ultrastructural changes that occur over time in cattle experimentally challenged with LSDV. Four calves were inoculated with wildtype LSDV and monitored for 19 to 21 days. At 7 days after inoculation, 2 of the 4 cattle developed multifocal cutaneous nodules characteristic of LSD. Some lesions displayed a targetoid appearance. Histologically, intercellular and intracellular edema was present in the epidermis of some nodules. Occasional intracytoplasmic inclusion bodies were identified in keratinocytes. More severe and consistent changes were present in the dermis, with marked histiocytic inflammation and necrotizing fibrinoid vasculitis of dermal vessels, particularly the deep dermal plexus. Chronic lesions consisted of full-thickness necrosis of the dermis and epidermis. Lesions in other body organs were not a major feature of LSD in this study, highlighting the strong cutaneous tropism of this virus. Immunohistochemistry and electron microscopy identified LSDV-infected histiocytes and fibroblasts in the skin nodules of affected cattle. This study highlights the noteworthy lesions of LSDV and how they develop over time.

Vaccines form the cornerstone of any control, eradication and preventative strategy and this is no different for lumpy skin disease. However, the usefulness of a vaccine is determined by a multiplicity of factors which include stability, efficiency, safety and ease of use, to name a few. Although the vaccination campaign in the Balkans against lumpy skin disease virus (LSDV) was successful and has been implemented with success in the past in other countries, data of vaccine failure have also been reported. It was therefore the purpose of this study to compare five homologous live attenuated LSDV vaccines (LSDV LAV) in a standardized setting. All five LSDV LAVs studied were able to protect against a challenge with virulent LSDV. Aside from small differences in serological responses, important differences were seen in side effects such as a local reaction and a Neethling response upon vaccination between the analyzed vaccines. These observations can have important implications in the applicability in the field for some of these LSDV LAVs.

From 2017 to 2019, several vaccine-like recombinant strains of lumpy skin disease virus (LSDV) were discovered in Kazakhstan and neighbouring regions of Russia and China. Shortly before their emergence, the authorities in Kazakhstan launched a mass vaccination campaign with the Neethling-based Lumpivax vaccine. Since none of the other countries in the affected region had used a homologous LSDV vaccine, it was soon suspected that the Lumpivax vaccine was the cause of these unusual LSDV strains. In this study, we performed a genome-wide molecular analysis to investigate the composition of two Lumpivax vaccine batches and to establish a possible link between the vaccine and the recent outbreaks. Although labelled as a pure Neethling-based LSDV vaccine, the Lumpivax vaccine appears to be a complex mixture of multiple CaPVs. Using an iterative enrichment/assembly strategy, we obtained the complete genomes of a Neethling-like LSDV vaccine strain, a KSGP-like LSDV vaccine strain and a Sudan-like GTPV strain. The same analysis also revealed the presence of several recombinant LSDV strains that were (almost) identical to the recently described vaccine-like LSDV strains. Based on their InDel/SNP signatures, the vaccine-like recombinant strains can be divided into four groups. Each group has a distinct breakpoint pattern resulting from multiple recombination events, with the number of genetic exchanges ranging from 126 to 146. The enormous divergence of the recombinant strains suggests that they arose during seed production. The recent emergence of vaccine-like LSDV strains in large parts of Asia is, therefore, most likely the result of a spillover from animals vaccinated with the Lumpivax vaccine.