Biology subjects

Hayes, B. H.

Publications and source records attributed to Hayes, B. H..

5 recordsLinked to original sources

bioRxiv2026

A modelling challenge to improve preparedness for highly pathogenicavian influenza epidemics: objectives, design and synthetic datageneration

Highly pathogenic avian influenza (HPAI) is among the most significant disease threats to poultry worldwide. Modelling challenges, where independent teams address a common epidemiological scenario, can support the development of response capabilities and strengthen communication between modellers and risk managers. Despite the established benefits of these exercises, they remain uncommon in animal health, and none have previously addressed avian influenza. Here Jolly Island, an artificial landscape of 9160 poultry farms with five production types, was developed and seeded with stochastic HPAI epidemics that ran their course over a three-to-four month period. From January through April 2026, 45 registered teams across five continents investigated a selected synthetic epidemic, producing probabilistic forecasts, inferring transmission drivers, and evaluating counterfactual control policies. Here the objectives, design choices, and data generation of the HPAI Modelling Challenge are described in full, covering transmission processes, surveillance system operations, and control strategy implementation, along with the selected epidemic trajectory, the narrative situation reports supplied to the teams at each phase, and the complete phase-specific datasets released to them. As the opening paper of this special issue, here is provided the foundation upon which all subsequent contributions, where teams document their approaches and analyses, are built.

ecology↗

bioRxiv2024

A multi-host mechanistic model of African swine fever emergence and control in Romania

African swine fever (ASF) has devastating effects on swine production, farmer livelihood, animal welfare, and biodiversity. Extremely difficult to control, epidemic management is further complicated when spillover between domestic pig and wild boar populations is suspected. To quantify ASF viral transmission between domestic pigs and wild boar, a spatially-explicit stochastic mechanistic model was constructed using village centroids to represent aggregated backyard pig herds and a hexagonal raster of forest coverage to represent wild boar abundance. The model was parameterized to the initial six months of the ongoing Romanian epidemic through approximate Bayesian computation. It was estimated that a median of 69.4% (interquartile range: 53.0-80.0%) of domestic pig herd cases came from other infected domestic pig herds while 20.4% (11.2-33.8%) originated from infected wild boar sources, and 8.4% (4.7-14.2%) stemmed from external sources not explicitly represented. Also, 31.9% of infected wild boar habitat (16.7-56.2%) originated from domestic pig herds and 68.1% (43.8-83.3%) came from neighboring infected wild boar populations. Furthermore, it was found that habitats with a forest coverage greater than 15% were 2.6 times more infectious and 5.3 times more susceptible than other habitats. All alternative control scenarios, including culling domestic pig herds upon local domestic pig or wild boar case detection, improved epidemic outcomes, with the greatest decrease in final epidemic size being observed from the reactive culling of entire villages following case detection. These results can be used to further inform policy recommendations in ASF-epidemic regions. Significance StatementThe current African swine fever (ASF) pandemic is devastating to affected nations, and quantifying transmission parameters is critical to informing control strategies. Disease spillover between wild and domestic hosts further complicates control efforts, yet the influence of spillover events on epidemic propagation remains unknown. Using the context of Romania--one of the European nations with the most severe epidemic and where spillover transmission is strongly suspected--we show that targeting spillover mechanisms is critical for achieving holistic disease control, and then demonstrate the impact of alternative control scenarios had they been enacted. These results can inform control strategy policy decisions in the many nations at-risk for or actively experiencing ASF epidemics.

ecology↗

bioRxiv2023

Chromosomal instability can favor macrophage-mediated immune response and induce a broad, vaccination-like anti-tumor IgG response

Chromosomal instability (CIN), a state in which cells undergo mitotic aberrations that generate chromosome copy number variations, generates aneuploidy and is thought to drive cancer evolution. Although associated with poor prognosis and reduced immune response, CIN generates aneuploidy-induced stresses that could be exploited for immunotherapies. In such contexts, macrophages and the CD47-SIRP checkpoint are understudied. Here, CIN is induced pharmacologically induced in poorly immunogenic B16F10 mouse melanoma cells, generating persistent micronuclei and diverse aneuploidy while skewing macrophages towards an anti-cancer M1-like phenotype, based on RNA-sequencing profiling, surface marker expression and short-term antitumor studies. These results further translate to in vivo efficacy: Mice bearing CIN-afflicted tumors with wild-type CD47 levels survive only slightly longer relative to chromosomally stable controls, but long-term survival is maximized when combining macrophage-stimulating anti-tumor IgG opsonization and some form of disruption of the CD47-SIRP checkpoint. Survivors make multi-epitope, de novo anti-cancer IgG that promote macrophage-mediated phagocytosis of CD47 knockout B16F10 cells and suppress tumoroids in vitro and growth of tumors in vivo. CIN does not greatly affect the level of the IgG response compared to previous studies but does significantly increase survival. These results highlight an unexpected therapeutic benefit from CIN when paired with maximal macrophage anti-cancer activity: an anti-cancer vaccination-like antibody response that can lead to more durable cures and further potentiate cell-mediated acquired immunity.

cancer biology↗

bioRxiv2022

Titrating CD47 by mismatch CRISPRi reveals incomplete repression can eliminate IgG-opsonized tumors but CD47 heterogeneity limits induction of anti-tumor IgG

Phagocytic elimination of solid tumors is an attractive mechanism for immunotherapy - particularly because of the possible induction of anti-cancer immunity. The phagocytic potential of macrophages is limited, however, by the CD47-SIRP checkpoint, and how much CD47 disruption is needed for efficacy remains unclear, even when tumors are opsonized by a pro-phagocytic antibody. Here, CRISPR-interference (CRISPRi) is applied with a large set of sgRNAs to produce a broad range of CD47 knockdowns in B16F10 melanoma, which is generally found to be resistant to the heavily studied PD-1 blockade. Guided by 3D immuno-tumoroid results, we identify a critical CD47 density below which macrophage-mediated phagocytosis dominates proliferation in the presence of an otherwise ineffective pro-phagocytic antibody (anti-Tyrp1). Growing tumors and immuno-tumoroids generally show selection for CD47-positive cells, but some mice reject tumors having >97% mean repression of CD47 or even having 80% repression - unless mixed with 50% repressed cells. Interestingly, long-term survivors have de novo pro-phagocytic IgG antibodies that increase in titer with depth of repression and also with early accumulation of tumor macrophages. Given well-known limitations of antibody permeation into solid tumors, our studies set a benchmark for anti-CD47 blockade and suggest deep disruption favors acquired immunity.

cancer biology↗

bioRxiv2022

Cooperative phagocytosis underlies macrophage immunotherapy of solid tumours and initiates a broad anti-tumour IgG response

Macrophages are abundant in solid tumours and typically associate with poor prognosis, but macrophage clusters in tumour nests have also been reported as beneficial even though dispersed macrophages would have more contacts with cancer cells. Here, by maximizing both phagocytic activity and macrophage numbers, we discover cooperative phagocytosis by low entropy clusters in rapidly growing engineered immuno-tumouroids. The results fit the calculus of proliferation-versus-engulfment, and rheological measurements and molecular perturbations provide a basis for understanding phagocytic disruption of a tumours cohesive forces in soft cellular phases. The perturbations underscore the utility of suppressing a macrophage checkpoint in combination with an otherwise ineffective tumour-opsonizing monoclonal antibody, and the approach translates in vivo to tumour elimination that durably protects mice from re-challenge and metastasis. Adoptive transfer of engineered macrophages increases the fraction of mice that eliminate tumours and potentially overcomes checkpoint blockade challenges in solid tumours like insufficient permeation of blocking antibodies and on-target, off-tumour binding. Finally, anti-cancer IgG induced in vivo are tumour-specific but multi-epitope and contribute to a phagocytic feedback that drives macrophage clustering in vitro. Given that solid tumours remain challenging for immunotherapies, durable anti-tumour responses here illustrate unexpected advantages in maximizing net phagocytic activity.

bioengineering↗