Zoonotic spillover, which is the transmission of a pathogen from a vertebrate animal to a human, presents a global public health burden but is a poorly understood phenomenon. Zoonotic spillover requires several factors to align, including the ecological, epidemiological and behavioural determinants of pathogen exposure, and the within-human factors that affect susceptibility to infection. In this Opinion article, we propose a synthetic framework for animal-to-human transmission that integrates the relevant mechanisms. This framework reveals that all zoonotic pathogens must overcome a hierarchical series of barriers to cause spillover infections in humans. Understanding how these barriers are functionally and quantitatively linked, and how they interact in space and time, will substantially improve our ability to predict or prevent spillover events. This work provides a foundation for transdisciplinary investigation of spillover and synthetic theory on zoonotic transmission.

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Pathways to zoonotic spillover

Vaccinia virus, no longer required for immunization against smallpox, now serves as a unique vector for expressing genes within the cytoplasm of mammalian cells. As a research tool, recombinant vaccinia viruses are used to synthesize and analyze the structure-function relationships of proteins, determine the targets of humoral and cell-mediated immunity, and investigate the types of immune response needed for protection against specific infectious diseases and cancer. The vaccine potential of recombinant vaccinia virus has been realized in the form of an effective oral wild-life rabies vaccine, although no product for humans has been licensed. A genetically altered vaccinia virus that is unable to replicate in mammalian cells and produces diminished cytopathic effects retains the capacity for high-level gene expression and immunogenicity while promising exceptional safety for laboratory workers and potential vaccine recipients.

https://www.pnas.org/content/pnas/93/21/11341.full.pdf

Genetically engineered poxviruses for recombinant gene expression, vaccination, and safety

The major goals of veterinary vaccines are to improve the health and welfare of companion animals, increase production of livestock in a cost-effective manner, and prevent animal-to-human transmission from both domestic animals and wildlife. These diverse aims have led to different approaches to the development of veterinary vaccines from crude but effective whole-pathogen preparations to molecularly defined subunit vaccines, genetically engineered organisms or chimeras, vectored antigen formulations, and naked DNA injections. The final successful outcome of vaccine research and development is the generation of a product that will be available in the marketplace or that will be used in the field to achieve desired outcomes. As detailed in this review, successful veterinary vaccines have been produced against viral, bacterial, protozoal, and multicellular pathogens, which in many ways have led the field in the application and adaptation of novel technologies. These veterinary vaccines have had, and continue to have, a major impact not only on animal health and production but also on human health through increasing safe food supplies and preventing animal-to-human transmission of infectious diseases. The continued interaction between animals and human researchers and health professionals will be of major importance for adapting new technologies, providing animal models of disease, and confronting new and emerging infectious diseases.

Current Status of Veterinary Vaccines

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Managing vertebrate pests: foxes.

Many pathogens, such as the agents of West Nile encephalitis and plague, are maintained in nature by animal reservoirs and transmitted to humans by arthropod vectors. Efforts to reduce disease incidence usually rely on vector control or immunization of humans. Lyme disease, for which no human vaccine is currently available, is a commonly reported vector-borne disease in North America and Europe. In a recently developed, ecological approach to disease prevention, we intervened in the natural cycle of the Lyme disease agent (Borrelia burgdorferi) by immunizing wild white-footed mice (Peromyscus leucopus), a reservoir host species, with either a recombinant antigen of the pathogen, outer surface protein A, or a negative control antigen in a repeated field experiment with paired experimental and control grids stratified by site. Outer surface protein A vaccination significantly reduced the prevalence of B. burgdorferi in nymphal blacklegged ticks (Ixodes scapularis) collected at the sites the following year in both experiments. The magnitude of the vaccine's effect at a given site correlated with the tick infection prevalence found on the control grid, which in turn correlated with mouse density. These data, as well as differences in the population structures of B. burgdorferi in sympatric ticks and mice, indicated that nonmouse hosts contributed more to infecting ticks than previously expected. Thus, where nonmouse hosts play a large role in infection dynamics, vaccination should be directed at additional species.

An ecological approach to preventing human infection: Vaccinating wild mouse reservoirs intervenes in the Lyme disease cycle

Rabies infection of domestic and wild animals is a serious problem throughout the world. The major disease vector in Europe is the red fox (Vulpes vulpes) and rabies control has focused on vaccinating and/or culling foxes. Culling has not been effective, and the distribution of five vaccine baits is the only appropriate method for the vaccination of wild foxes. Although some European countries have conducted field vaccination campaigns using attenuated rabies virus strains, their use has not been extensively approved because they retain pathogenicity for rodents and can revert to virulence. These strains cannot be used in North America because they are pathogenic for the striped skunk (Mephitis mephitis) and are ineffective in the raccoon (Procyon lotor). We have constructed a recombinant vaccinia virus, VVTGgRAB, expressing the surface glycoprotein (G) of rabies virus (ERA strain). The recombinant was a highly effective vaccine in experimental animals, in captive foxes and in raccoons. We report here the results of a large-scale campaign of fox vaccination in a 2,200 km2 region of southern Belgium, an area in which rabies is prevalent. After distribution, 81% of foxes inspected were positive for tetracycline, a biomarker included in the vaccine bait and, other than one rabid fox detected close to the periphery of the treated area, no case of rabies, either in foxes or in domestic livestock, has been reported in the area.

/pdf/large-scale-eradication-of-rabies-using-recombinant-vaccinia-1enc1xngol.pdf

Large-scale eradication of rabies using recombinant vaccinia-rabies vaccine

Lutte contre la rage en Belgique: bilan épidémiologique 1991 et stratégie future

African pangolins are currently experiencing unprecedented levels of harvesting, feeding both local demands and the illegal international trade. So far, the lack of knowledge on the population genetics of African pangolins has hampered any attempts at assessing their demographic status and tracing their trade at the local scale. We conducted a pioneer study on the genetic tracing of the African pangolin trade in the Dahomey Gap (DG). We sequenced and genotyped 189 white-bellied pangolins from 18 forests and 12 wildlife markets using one mitochondrial fragment and 20 microsatellite loci.Tree-based assignment procedure showed that the pangolin trade is endemic to the DG region, as it was strictly fed by the the Dahomey Gap lineage (DGL). DGL populations were characterized by low levels of genetic diversity, an overall absence of equilibrium, important inbreeding levels, and lack of geographic structure. We identified a 92-98% decline in DGL effective population size 200-500 ya-concomitant with major political transformations along the 'Slave Coast'-leading to contemporaneous estimates being inferior to minimum viable population size (< 500). Genetic tracing suggested that wildlife markets from the DG sourced pangolins through the entire DGL range. Our loci provided the necessary power to distinguish among all the genotyped pangolins, tracing the dispatch of a same individual on the markets and within local communities. We developed an approach combining rarefaction analysis of private allele frequencies with cross-validation of observed data that traced five traded pangolins to their forest origin, c. 200-300 km away from the markets.Although the genetic toolkit that we designed from traditional markers can prove helpful to trace the illegal trade in pangolins, our tracing ability was limited by the lack of population structure within the DGL. Given the deleterious combination of genetic, demographic, and trade-related factors affecting DGL populations, the conservation status of white-bellied pangolins in the DG should be urgently re-evaluated. 

/pdf/can-dna-help-trace-the-local-trade-of-pangolins-conservation-2inbts7o.pdf

Can DNA help trace the local trade of pangolins? Conservation genetics of white-bellied pangolins from the Dahomey Gap (West Africa)

https://bmcecolevol.biomedcentral.com/track/pdf/10.1186/s12862-022-01971-5

Komlan Afiademanyo

Papers

Large-scale eradication of rabies using recombinant vaccinia-rabies vaccine

Lutte contre la rage en Belgique: bilan épidémiologique 1991 et stratégie future

Can DNA help trace the local trade of pangolins? Conservation genetics of white-bellied pangolins from the Dahomey Gap (West Africa)

Can DNA help trace the local trade of pangolins? Conservation genetics of white-bellied pangolins from the Dahomey Gap (West Africa)