Lumpy skin disease, sheeppox, and goatpox are notifiable diseases of cattle, sheep, and goats, respectively, caused by viruses of the Capripoxvirus genus. They are responsible for both direct and indirect financial losses. These losses arise through animal mortality, morbidity cost of vaccinations, and constraints to animals and animal products’ trade. Control and eradication of capripoxviruses depend on early detection of outbreaks, vector control, strict animal movement, and vaccination which remains the most effective means of control. To date, live attenuated vaccines are widely used; however, conferred protection remains controversial. Many vaccines have been associated with adverse reactions and incomplete protection in sheep, goats, and cattle. Many combination- and recombinant-based vaccines have also been developed. Here, we review capripoxvirus infections and the immunity conferred against capripoxviruses by their respective vaccines for each ruminant species. We also review their related cross protection to heterologous infections.

Lumpy skin disease virus (LSDV), a Capripoxvirus, is of economic importance in the cattle industry and is controlled by vaccination. A comparison was made of the host response to the two LSDV vaccines Neethling and Herbivac LS, with reference to the well-studied Orthopoxvirus, modified vaccinia Ankara (MVA), in a mouse model. Because the vaccines differ at the superoxide dismutase homologue (SOD) gene locus, recombinant SOD knock-out and knock-in nLSDV vaccines were constructed and all four vaccines were tested for the induction and inhibition of apoptosis. The SOD homologue was associated both with induction of apoptosis as well as inhibition of camptothecin-induced apoptosis. Histological analysis of chorioallantoic membranes of fertilized hens’ eggs infected with the four different vaccines indicated marked mesodermal proliferation associated with vaccines containing the full-length SOD homologue as well as increased immune cell infiltration. Our findings suggest that the SOD homologue may influence vaccine immunogenicity.

Dual vaccines (n = 6) against both lumpy skin disease (LSD) and bovine ephemeral fever (BEF) were constructed, based on the BEFV glycoprotein (G) gene, with or without the BEFV matrix (M) protein gene, inserted into one of two different LSDV backbones, nLSDV∆SOD-UCT or nLSDVSODis-UCT. The inserted gene cassettes were confirmed by PCR; and BEFV protein was shown to be expressed by immunofluorescence. The candidate dual vaccines were initially tested in a rabbit model; neutralization assays using the South African BEFV vaccine (B-Phemeral) strain showed an African consensus G protein gene (Gb) to give superior neutralization compared to the Australian (Ga) gene. The two LSDV backbones expressing both Gb and M BEFV genes were tested in cattle and shown to elicit neutralizing responses to LSDV as well as BEFV after two inoculations 4 weeks apart. The vaccines were safe in cattle and all vaccinated animals were protected against virulent LSDV challenge, unlike a group of control naïve animals, which developed clinical LSD. Both neutralizing and T cell responses to LSDV were stimulated upon challenge. After two inoculations, all vaccinated animals produced BEFV neutralizing antibodies ≥ 1/20, which is considered protective for BEF.

The host’s immune status may affect virus evolution. Little is known about how developing fetal and placental immune milieus affect virus heterogeneity. This knowledge will help us better understand intra-host virus evolution and how new virus variants emerge. The goal of our study was to find out whether the isolated in utero environment—an environment with specialized placental immunity and developing fetal immunity—supports the emergence of RNA and DNA virus variants. We used well-established porcine models for isolated Zika virus (RNA virus) and porcine circovirus 2 (DNA virus) fetal infections. We found that the isolated in utero environment was conducive to the emergence of RNA and DNA virus variants. Next-generation sequencing of nearly whole virus genomes and validated bioinformatics pipelines identified both unique and convergent single nucleotide variations in virus genomes isolated from different fetuses. Zika virus and PCV2 in utero evolution also resulted in single nucleotide variations previously reported in the human and porcine field samples. These findings should encourage further studies on virus evolution in placenta and fetuses, to better understand how virus variants emerge and how in utero viral evolution affects congenital virus transmission and pathogenicity.

Lumpy skin disease virus (LSDV) causes severe disease in cattle and water buffalo and is transmitted by hematophagous arthropod vectors. Detailed information of the adaptive and innate immune response to LSDV is limited, hampering the development of tools to control the disease. This study provides an in-depth analysis of the immune responses of calves experimentally inoculated with LSDV via either needle-inoculation or arthropod-inoculation using virus-positive Stomoxys calcitrans and Aedes aegypti vectors. Seven out of seventeen needle-inoculated calves (41%) developed clinical disease characterised by multifocal necrotic cutaneous nodules. In comparison 8/10 (80%) of the arthropod-inoculated calves developed clinical disease. A variable LSDV-specific IFN-γ immune response was detected in the needle-inoculated calves from 5 days post inoculation (dpi) onwards, with no difference between clinical calves (developed cutaneous lesions) and nonclinical calves (did not develop cutaneous lesions). In contrast a robust and uniform cell-mediated immune response was detected in all eight clinical arthropod-inoculated calves, with little response detected in the two nonclinical arthropod-inoculated calves. Neutralising antibodies against LSDV were detected in all inoculated cattle from 5-7 dpi. Comparison of the production of anti-LSDV IgM and IgG antibodies revealed no difference between clinical and nonclinical needle-inoculated calves, however a strong IgM response was evident in the nonclinical arthropod-inoculated calves but absent in the clinical arthropod-inoculated calves. This suggests that early IgM production is a correlate of protection in LSD. This study presents the first evidence of differences in the immune response between clinical and nonclinical cattle and highlights the importance of using a relevant transmission model when studying LSD.