Dascalu S, Geambasu O, Covaciu O, Chereches R M, Diaconu G, Dumitra G G, Gheorghita V, Popovici E D (2021)

Prospects of COVID-19 vaccination in Romania: challenges and potential solutions

Frontiers in Public Health 9, 644538

Abstract

The rapid advancement in vaccine development represents a critical milestone that will help humanity tackle the COVID-19 pandemic. However, the success of these efforts is not guaranteed, as it relies on the outcomes of national and international vaccination strategies. In this article, we highlight some of the challenges that Romania will face and propose a set of solutions to overcome them. With this in mind, we discuss issues such as the infrastructure of vaccine storage and delivery, the deployment and administration of immunisations, and the public acceptance of vaccines. The ways in which Romanian society will respond to a national COVID-19 vaccination campaign will be contingent on appropriate and timely actions. As many of the problems encountered in Romania are not unique, the proposed recommendations could be adapted and implemented in other countries that face similar issues, thereby informing better practices in the management of the COVID-19 pandemic.

Abstract

Interpreting the interplay between politics, social demographics and epidemiology is essential for understanding how a disease's occurrence and control evolve over time. Foot-and-mouth disease (FMD) virus was first detected in Kenya in 1915 and serotyped in 1932. This review aims to describe and appraise initiatives to control FMD in Kenya since its independence from British rule in 1964, using information from the scientific literature. We describe the historical dynamics of FMD epidemiology in the country and determine socio-political factors that have shaped the control strategies used. PubMed, Scopus, CAB abstracts, Science Direct, Web of Science and Google Scholar were used to search and retrieve papers, using predetermined search criteria encompassing FMD, Kenya and disease control programme descriptors. In total 1234 papers were identified and screened for relevance using the World Health Organization's guidelines for rapid review. Ultimately 69 references from this search were included, and information extracted and consolidated. These papers highlight that following independence, there was a structured effort to control FMD consisting of a compulsory subsidised vaccination programme in the Rift Valley with movement controls and quarantine when outbreaks occurred. This programme led to an initial decrease in recorded FMD outbreaks. However, endemic circulation continued and this programme was discontinued due to multiple factors, including political deprioritisation and changes in the structure of veterinary services. Only low levels of active surveillance have been applied since 1964; most surveillance is passive and relies on outbreak reports. Currently control focuses on outbreak management and a mixture of public- and privately-funded vaccination. This review highlights critical drivers influencing disease control programme implementation including veterinary service structure, the active participation of stakeholders with farming systems and availability of affordable and matched FMD vaccine. Additionally, it appraises the availability of historical information and draws attention to gaps in the historical record.

Cockerill G S, Angell R M, Bedernjak A, Chuckowree I, Fraser I a, Gascon-Simorte J, Gilman M S A, Good J A D, Harland R, Johnson S M, Ludes-Meyers J H, Littler E, Lumley J, Lunn G, Mathews N, McLellan J S, Paradowski M, Peeples M E, Scott C, Tait D, Taylor G, Thom M, Thomas E, Villalonga Barber C, Ward S E, Watterson D, Williams G, Young P, Powell K (2021)

Discovery of Sisunatovir (RV521), an inhibitor of respiratory syncytial virus fusion

Journal of Medicinal Chemistry early view

Abstract

RV521 is an orally bioavailable inhibitor of respiratory syncytial virus (RSV) fusion that was identified after a lead optimization process based upon hits that originated from a physical property directed hit profiling exercise at Reviral. This exercise encompassed collaborations with a number of contract organizations with collaborative medicinal chemistry and virology during the optimization phase in addition to those utilized as the compound proceeded through preclinical and clinical evaluation. RV521 exhibited a mean IC50 of 1.2 nM against a panel of RSV A and B laboratory strains and clinical isolates with antiviral efficacy in the Balb/C mouse model of RSV infection. Oral bioavailability in preclinical species ranged from 42 to >100% with evidence of highly efficient penetration into lung tissue. In healthy adult human volunteers experimentally infected with RSV, a potent antiviral effect was observed with a significant reduction in viral load and symptoms compared to placebo.

Bakshy K, Heimeier D, Schwartz J C, Glass E J, Wilkinson S, Skuce R A, Allen A R, Young J, McClure J C, Cole J B, Null D J, Hammond J A, Smith T P L, Bickhart D M (2021)

Development of polymorphic markers in the immune gene complex loci of cattle

Journal of Dairy Science 104 (5)

Abstract

The addition of cattle health and immunity traits to genomic selection indices holds promise to increase individual animal longevity and productivity, and decrease economic losses from disease. However, highly variable genomic loci that contain multiple immune-related genes were poorly assembled in the first iterations of the cattle reference genome assembly and underrepresented during the development of most commercial genotyping platforms. As a consequence, there is a paucity of genetic markers within these loci that may track haplotypes related to disease susceptibility. By using hierarchical assembly of bacterial artificial chromosome inserts spanning 3 of these immune-related gene regions, we were able to assemble multiple full-length haplotypes of the major histocompatibility complex, the leukocyte receptor complex, and the natural killer cell complex. Using these new assemblies and the recently released ARS-UCD1.2 reference, we aligned whole-genome shotgun reads from 125 sequenced Holstein bulls to discover candidate variants for genetic marker development. We selected 124 SNPs, using heuristic and statistical models to develop a custom genotyping panel. In a proof-of-principle study, we used this custom panel to genotype 1,797 Holstein cows exposed to bovine tuberculosis (bTB) that were the subject of a previous GWAS study using the Illumina BovineHD array. Although we did not identify any significant association of bTB phenotypes with these new genetic markers, 2 markers exhibited substantial effects on bTB phenotypic prediction. The models and parameters trained in this study serve as a guide for future marker discovery surveys particularly in previously unassembled regions of the cattle genome.

Waters R A, Wadsworth J, Mioulet V, Shaw A E, Knowles N J, Abdollahi D, Hassanzadeh R, Sumption K, King D P (2021)

Foot-and-mouth disease virus infection in the domestic dog (Canis lupus familiaris), Iran

BMC Veterinary Research 17 (1), 63

Abstract

Background: Foot-and-mouth disease (FMD) is a highly infectious viral disease, recognised to affect animals in the order Artiodactyla. The disease is rarely fatal in adult animals, however high mortality is associated with neonatal and juvenile infection.

Case presentation: Five puppies died after being fed lamb carcases, the lambs having died during an outbreak of FMD in Iran. Following a post-mortem examination, cardiac tissue from one of the dead puppies was subjected to virus isolation, antigen ELISA, real-time RT-PCR, sequencing and confocal microscopy to assess the presence and characteristics of any FMD virus. The virological and microscopic examination of the cardiac tissue provided evidence of FMD virus replication in the canine heart.

Conclusions: The data generated in this study demonstrate for the first time that FMD virus can internalise and replicate in dogs and may represent an epidemiologically significant event in FMD transmission, highlighting the dangers of feeding diseased animal carcases to other species. The reporting of this finding may also focus attention on similar disease presentations in dogs in FMD endemic countries allowing a better understanding of the prevalence of such events.

Abstract

Processing and packaging of herpesvirus genomic DNA is regulated by a packaging-associated terminase complex comprising of viral proteins pUL15, pUL28 and pUL33. Marek’s disease virus (MDV) homologs UL28 and UL33 showed conserved functional features with high sequence identity with the corresponding Herpes simplex virus 1 (HSV-1) homologs. As part of the investigations into the role of the UL28 and UL33 homologs of oncogenic MDV for DNA packaging and replication in cultured cells, we generated MDV mutant clones deficient in UL28 or UL33 of full-length MDV genomes. Transfection of UL28- or UL33-deleted BAC DNA into chicken embryo fibroblast (CEF) did not result either in the production of visible virus plaques, or detectable single cell infection after passaging onto fresh CEF cells. However, typical MDV plaques were detectable in CEF transfected with the DNA of revertant mutants where the deleted genes were precisely reinserted. Moreover, the replication defect of the UL28-deficient mutant was completely restored when fragment encoding the full UL28 gene was co-transfected into CEF cells. Viruses recovered from the revertant construct, as well as by the UL28 co-transfection, showed replication ability comparable with parental virus. Furthermore, the transmission electron microscopy study indicated that immature capsids were assembled without the UL28 expression, but with the loss of infectivity. Importantly, predicted three-dimensional structures of UL28 between MDV and HSV-1 suggests conserved function in virus replication. For the first time, these results revealed that both UL28 and UL33 are essential for MDV replication through regulating DNA cleavage and packaging.

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