An Attenuated Vaccine Virus of the Neethling Lineage Protects Cattle against the Virulent Recombinant Vaccine-like Isolate of the Lumpy Skin Disease Virus Belonging to the Currently Established Cluster 2.5.

Lumpy skin disease (LSD) is an emerging transboundary and highly infectious viral disease mainly affecting cattle. The fact that it was initially confined to Africa and then spread beyond its geographical range to other regions, including the Middle East, Turkey, Europe, the Balkans, Russia and Asia, is an indication of the underestimation and neglect of this disease. Vaccination is considered the most effective way to control the spread of LSDV, when combined with other control measures. LSD is now on the rise in Southeast Asia, where the circulating virus belongs to recombinant lineage 2.5. In this study, we evaluated the efficacy of an attenuated LSDV strain belonging to the Neethling cluster 1.1 by challenge with a virulent recombinant vaccine-like LSDV isolate "Mongolia/2021" belonging to cluster 2.5. Some of the vaccinated animals showed an increase in body temperature of 1-1.5 °C above the physiological norm, without clinical signs, local reactions, vaccine-induced viremia or generalization, demonstrating the efficacy and safety of the vaccine strain against a recombinant strain. Furthermore, all the vaccinated animals showed strong immune responses, indicating a high level of immunogenicity. However, the control group challenged with "Mongolia/2021" LSD showed moderate to severe clinical signs seen in an outbreak, with high levels of virus shedding in blood samples and nasal swabs. Overall, the results of the present study demonstrate that the attenuated LSDV Neethling strain vaccine has a promising protective phenotype against the circulating strains, suggesting its potential as an effective tool for the containment and control of LSD in affected countries from Southeast Asia.

Subclinical infection caused by a recombinant vaccine-like strain poses high risks of lumpy skin disease virus transmission.

Lumpy skin disease (LSD) is a transboundary viral infection, affecting cattle with characteristic manifestations involving multiple body systems. A distinctive characteristic of lumpy skin disease is the subclinical disease manifestation wherein animals have viremia and shed the virus through nasal and ocular discharges, while exhibiting no nodules but enlarged lymph nodes that are easily oversighted by inexperienced vets. Further research on the role of subclinically ill animals in the transmission of LSD virus (LSDV) can contribute to the development of more effective tools to control the disease worldwide. Thus, this study aims to determine the potential role of subclinical infection in virus transmission in a non-vector-borne manner. To achieve this, we inoculated animals with the recombinant vaccine-like strain (RVLS) Udmurtiya/2019 to cause clinical and subclinical LSDV infection. After the disease manifestation, we relocated the subclinically ill animals to a new clean facility followed by the introduction of another five animals to determine the role of RVLS-induced subclinical infection in the virus transmission via direct/indirect contact. After the introduction of the naïve animals to the relocated subclinically ill ones in a shared airspace, two introduced animals contracted the virus (clinically and subclinically), showing symptoms of fever, viremia, and seroconversion in one animal, while three other introduced animals remained healthy and PCR-negative until the end of the study. In general, the findings of this study suggest the importance of considering LSDV subclinical infection as a high-risk condition in disease management and outbreak investigations.

The Live Attenuated Vaccine Strain "ARRIAH" Completely Protects Goats from a Virulent Lineage IV Field Strain of Peste Des Petits Ruminants Virus.

Peste des petits ruminants (PPR) is a transboundary viral disease that affects small ruminants, such as goats and sheep, in Africa, the Middle East, and Asia, causing substantial damage to livelihoods and disrupting livestock trade. Although Russia is PPR virus (PPRV)-free, controlling PPRV in neighboring countries is the top national priority. Recent PPR outbreaks in Mongolia and other countries in the Middle East caused by a lineage IV virus represent a risk of transboundary emergence in neighboring countries, including China, Kazakhstan, and Russia. In the present study, we assessed the potency and safety of the ARRIAH live attenuated PPRV vaccine (lineage II) in Zaannen and Nubian goat breeds by challenging them with a virulent lineage IV Mongolia/2021 isolate. For comparison, two commercial vaccines of Nigeria75/1 strain were used. The ARRIAH-vaccinated animals showed an increase in body temperature of 1-1.5 °C above the physiological norm, similar to the animals vaccinated with Nigeria75/1 vaccines. In all vaccinated groups, the average rectal temperature never exceeded 39.4-39.7 °C throughout the infection period, and no clinical signs of the disease were observed, demonstrating vaccine efficacy and safety in the current experimental setting. However, the control group (mock vaccinated) challenged with Mongolia/2021 PPRV exhibited moderate-to-severe clinical signs. Overall, the findings of the present study demonstrate that the ARRIAH vaccine strain has a promising protective phenotype compared with Nigeria75/1 vaccines, suggesting its potential as an effective alternative for curbing and controlling PPR in affected countries. Although the ARRIAH vaccine against PPR is not currently endorsed by the World Organization for Animal Health due to its incomplete safety and potency profile, this study is the first step to provide experimentally validated data on the ARRIAH vaccine.

A Recombinant Vaccine-like Strain of Lumpy Skin Disease Virus Causes Low-Level Infection of Cattle through Virus-Inoculated Feed.

Since 1989, lumpy skin disease of cattle (LSD) has spread out of Africa via the Middle East northwards and eastwards into Russia, the Far East and South-East Asia. It is now threatening to become a worldwide pandemic, with Australia possibly next in its path. One of the research gaps on the disease concerns its main mode of transmission, most likely via flying insect vectors such as biting flies or mosquitoes. Direct or indirect contact transmission is possible, but appears to be an inefficient route, although there is evidence to support the direct contact route for the newly detected recombinant strains first isolated in Russia. In this study, we used experimental bulls and fed them via virus-inoculated feed to evaluate the indirect contact route. To provide deeper insights, we ran two parallel experiments using the same design to discover differences that involved classical field strain Dagestan/2015 LSDV and recombinant vaccine-like Saratov/2017. Following the attempted indirect contact transmission of the virus from the inoculated feed via the alimentary canal, all bulls in the Dagestan/2015 group remained healthy and did not seroconvert by the end of the experiment, whereas for those in the Saratov/2017 recombinant virus group, of the five bulls fed on virus-inoculated feed, three remained clinically healthy, while two displayed evidence of a mild infection. These results provide support for recombinant virus transmission via the alimentary canal. In addition, of particular note, the negative control in-contact bull in this group exhibited a biphasic fever at days 10 and 20, developed lesions from day 13 onwards, and seroconverted by day 31. Two explanations are feasible here: one is the in-contact animal was somehow able to feed on some of the virus-inoculated bread left over from adjacent animals, but in the case here of the individual troughs being used, that was not likely; the other is the virus was transmitted from the virus-fed animals via an airborne route. Across the infected animals, the virus was detectable in blood from days 18 to 29 and in nasal discharge from days 20 to 42. Post-mortem and histological examinations were also indicative of LSDV infection, supporting further evidence for rapid, in F transmission of this virus. This is the first report of recombinant LSDV strain transmitting via the alimentary mode.

The changing epidemiology of lumpy skin disease in Russia since the first introduction from 2015 to 2020.

Lumpy skin disease (LSD) is an economically important transboundary disease affecting cattle, causing large economic losses such as decreased production and trade restrictions. LSD has been a historically neglected disease since it previously caused disease limited to the African continent. Currently, the epidemiology of LSD virus is based on how the disease is transmitted in tropical and sub-tropical climates. The understanding of its epidemiology in hemiboreal climates is not well understood and needs urgent attention to expand the current knowledge. In this study, the epidemiological findings on LSD in Russia over a 6-year period are summarized and discussed. A total of 471 outbreaks were identified spanning over a 9000 km range. The outbreaks of LSD occur primarily in small holder farms (backyard) compared to commercial farms between mid-May through mid-November including weather conditions with snow and freezing temperatures that preclude vector activity. Mortality and morbidity varied across the 6 years ranging from 1.19% to 61.8% and 0% to 50%, respectively, with a tendency to decline from 2015 to 2020. The geographic pattern of spread was assessed by means of directionality, indicating a northward movement from 2015 to 2016, with a consequent East turn in 2017 through Siberia to the Far East by 2020. All cases occurred along the border with Kazakhstan. Mathematical modelling showed that the disease tended to form statistically verified annual spatiotemporal clusters in 2016-2018, whereas in 2019 and 2020 such segregation was not evident. The trend of spread was mainly either from south to north or from south to a north-east direction.

A lumpy skin disease virus which underwent a recombination event demonstrates more aggressive growth in primary cells and cattle than the classical field isolate.

Genomic changes by recombination have been recently observed in lumpy skin disease viruses circulating in Russia. The first characterized naturally occurring recombinant lumpy skin disease virus Saratov/2017 occurred through recombination between a live attenuated virus vaccine and the Southern African lumpy skin disease virus. Understanding if recombination can increase or decrease virulence of viruses through changes in different gene regions is required to improve the understanding of capripoxvirus biology. In this study, the in vitro and in vivo growth of the recombinant Saratov/2017 and the classical field isolate Dagestan/2015 was compared. Primary lamb kidney and lamb testis cells as well as the goat ovarian cell line were used to assess virus replication. In the goat ovarian cell line, Saratov/2017 and Dagestan/2015 induced comparable cytopathic activity and virus titres. In contrast, in primary lamb kidney and lamb testis cells, Saratov/2017 grew more aggressively causing more massive rounding up of cells, detachment and agglomeration compared to Dagestan/20152015. Growth curves of Saratov/2017 and Dagestan/2015 were assessed in primary lamb testis cells using different multiplicities of infection (MOI), with Saratov/2017 demonstrating faster replication at the different MOI and time points evaluated post-infection. In cattle, Saratov/2017 demonstrated more pronounced skin reactions when titrated by skin inoculation of serially diluted virus. In both primary cells and cattle, the titre of Saratov/2017 was significantly higher compared to Dagestan/2015 (p ≤ .05). These results demonstrate recombinant Saratov/2017 exhibits more aggressive replication properties.

Full-length genome characterization of a novel recombinant vaccine-like lumpy skin disease virus strain detected during the climatic winter in Russia, 2019.

An uncharacteristic outbreak of lumpy skin disease was reported in the Republic of Udmurtiya, Russia, during the climatic winter of March 2019. The causative lumpy skin disease virus (LSDV_Udmurtiya_Russia_2019) was shown to be a recombinant composed of a live attenuated Neethling-type vaccine strain as the dominant parental strain and a Kenyan KSGP/NI-2490-like virus as its minor parental strain, with 24 statistically significant recombination events that are not identical to those in LSDV Saratov/2017, in which 27 events were identified.

Evidence of recombination of vaccine strains of lumpy skin disease virus with field strains, causing disease.

Vaccination against lumpy skin disease (LSD) is crucial for maintaining the health of animals and the economic sustainability of farming. Either homologous vaccines consisting of live attenuated LSD virus (LSDV) or heterologous vaccines consisting of live attenuated sheeppox or goatpox virus (SPPV/GPPV) can be used for control of LSDV. Although SPPV/GTPV-based vaccines exhibit slightly lower efficacy than live attenuated LSDV vaccines, they do not cause vaccine-induced viremia, fever, and clinical symptoms of the disease following vaccination, caused by the replication capacity of live attenuated LSDVs. Recombination of capripoxviruses in the field was a long-standing hypothesis until a naturally occurring recombinant LSDV vaccine isolate was detected in Russia, where the sheeppox vaccine alone is used. This occurred after the initiation of vaccination campaigns using LSDV vaccines in the neighboring countries in 2017, when the first cases of presumed vaccine-like isolate circulation were documented with concurrent detection of a recombinant vaccine isolate in the field. The follow-up findings presented herein show that during the period from 2015 to 2018, the molecular epidemiology of LSDV in Russia split into two independent waves. The 2015-2016 epidemic was attributable to the field isolate. Whereas the 2017 epidemic and, in particular, the 2018 epidemic represented novel disease importations that were not genetically linked to the 2015-2016 field-type incursions. This demonstrated a new emergence rather than the continuation of the field-type epidemic. Since recombinant vaccine-like LSDV isolates appear to have entrenched across the country's border, the policy of using certain live vaccines requires revision in the context of the biosafety threat it presents.