Longitudinal deep sequencing informs vector selection and future deployment strategies for transmissible vaccines

Abstract

Vaccination is a powerful tool in combating infectious diseases of humans and companion animals. In most wildlife, including reservoirs of emerging human diseases, achieving sufficient vaccine coverage to mitigate disease burdens remains logistically unattainable. Virally vectored “transmissible” vaccines that deliberately spread among hosts are a potentially transformative, but still theoretical, solution to the challenge of immunising inaccessible wildlife. Progress towards real-world application is frustrated by the absence of frameworks to guide vector selection and vaccine deployment prior to major in vitro and in vivo investments in vaccine engineering and testing. Here, we performed deep sequencing on field-collected samples of Desmodus rotundus betaherpesvirus (DrBHV), a candidate vector for a transmissible vaccine targeting vampire bat–transmitted rabies. We discovered 11 strains of DrBHV that varied in prevalence and geographic distribution across Peru. The phylogeographic structure of DrBHV strains was predictable from both host genetics and landscape topology, informing long-term DrBHV-vectored vaccine deployment strategies and identifying geographic areas for field trials where vaccine spread would be naturally contained. Multistrain infections were observed in 79% of infected bats. Resampling of marked individuals over 4 years showed within-host persistence kinetics characteristic of latency and reactivation, properties that might boost individual immunity and lead to sporadic vaccine transmission over the lifetime of the host. Further, strain acquisitions by already infected individuals implied that preexisting immunity and strain competition are unlikely to inhibit vaccine spread. Our results support the development of a transmissible vaccine targeting a major source of human and animal rabies in Latin America and show how genomics can enlighten vector selection and deployment strategies for transmissible vaccines.

Effects of culling vampire bats on the spatial spread and spillover of rabies virus

“…Preventive interventions are a greater challenge in VBR-enzootic areas where the locations of future outbreaks are less predictable; however, network models of rabies spread among bat colonies offer a promising way forward ( 40 ). Reproductive suppression and self-disseminating vaccines targeting vampire bats are emerging tools to manage both rabies and bat populations, which might diminish counterproductive effects of disturbance-induced dispersal on rabies spatial spread ( 41 – 43 ). Moreover, the disturbance-induced dispersal of bats following capture observed here might be exploited to benefit rabies prevention by promoting vaccine spread to nearby populations.…”

Ecological determinants of rabies virus dynamics in vampire bats and spillover to livestock

“…Landscape variables included: (1) ‘suitability’, calculated as the proportion of neighbouring cells assumed to be suitable for vampire bat presence (less than or equal 3600 m [ 17 ]) using CGIAR-SRTM 90-m resolution elevation data [ 32 ]; (2) ‘terrain ruggedness index’ (TRI), which is the relative difference between the elevation of a central cell and its eight surrounding cells [ 31 ] (slope and roughness were also computed but were highly correlated with TRI; electronic supplementary material, figure S1); (3) ‘livestock density,’ estimated as the average densities of horses, goats, pigs, sheep and cattle within 10 km of each bat site using the 2010 Gridded Livestock of the World, the highest resolution data available on livestock densities (5 min of arc resolution [ 33 ]); and (4) a ‘least-cost distance’ (LCD) measure of spatial isolation, assuming a model where movement costs increase linearly with elevation until 3600 m, then movement cost is infinite (i.e. a hard barrier to bat dispersal) [ 24 ]. We averaged LCDs from 20 randomly selected points located 40 km away (Euclidian distances) from each site.…”

“…Alternatively, prolonged incubation periods are well recognized in rabies and might enable epizootics following recovery of susceptible populations to threshold levels, generating patterns that might outwardly resemble extinction–recolonization dynamics driven by viral spatial spread [ 16 , 23 ]. Clarifying knowledge gaps surrounding VBRV maintenance might improve allocation of vaccines to spillover populations at greatest risk and guide strategies for vampire bat management [ 24 , 25 ]. For example, if VBRV is maintained locally, understanding environmental stressors on bats and managing susceptible bat populations below epizootic thresholds (by vaccination or culling) might mitigate its burden [ 12 , 16 ].…”

Quantifying spillover risk with an integrated bat-rabies dynamic modeling framework

“…Moreover, indiscriminate culling may lead to social disruptions in the roosts, which facilitates pathogen spread (Benavides et al, 2020;. As a less controversial alternative and arguably more effective, spreadable vaccine may be administrated in a similar manner (Standing et al, 2017;Bakker et al, 2019;Griffiths et al, 2022). Risk maps for each combination of current control measures used in the area of interest, the state of São Paulo, Brazil, are provided.…”