Poxvirus systems have been extensively used as vaccine vectors. Herein a RNA-Seq analysis of intramuscular injection sites provided detailed insights into host innate immune responses, as well as expression of vector and recombinant immunogen genes, after vaccination with a new multiplication defective, vaccinia-based vector, Sementis Copenhagen Vector. Chikungunya and Zika virus immunogen mRNA and protein expression was associated with necrosing skeletal muscle cells surrounded by mixed cellular infiltrates. The multiple adjuvant signatures at 12 hours post-vaccination were dominated by TLR3, 4 and 9, STING, MAVS, PKR and the inflammasome. Th1 cytokine signatures were dominated by IFNγ, TNF and IL1β, and chemokine signatures by CCL5 and CXCL12. Multiple signatures associated with dendritic cell stimulation were evident. By day seven, vaccine transcripts were absent, and cell death, neutrophil, macrophage and inflammation annotations had abated. No compelling arthritis signatures were identified. Such injection site vaccinology approaches should inform refinements in poxvirus-based vector design. Poxvirus vector systems have been widely developed for vaccine applications. Despite considerable progress, so far only one recombinant poxvirus vectored vaccine has to date been licensed for human use, with ongoing efforts seeking to enhance immunogenicity whilst minimizing reactogenicity. The latter two characteristics are often determined by early post-vaccination events at the injection site. We therefore undertook an injection site vaccinology approach to analyzing gene expression at the vaccination site after intramuscular inoculation with a recombinant, multiplication defective, vaccinia-based vaccine. This provided detailed insights into inter alia expression of vector-encoded immunoregulatory genes, as well as host innate and adaptive immune responses. We propose that such injection site vaccinology can inform rational vaccine vector design, and we discuss how the information and approach elucidated herein might be used to improve immunogenicity and limit reactogenicity of poxvirus-based vaccine vector systems.

Vascular wilt caused by the ascomycete fungal pathogen Fusarium oxysporum f. sp. cubense (Foc) is a major constraint of banana production around the world. The virulent race, namely Tropical Race 4, can infect all Cavendish-type banana plants and is now widespread across the globe, causing devastating losses to global banana production. In this study, we characterized Foc Subtropical Race 4 (STR4) resistance in a wild banana relative which, through estimated genome size and ancestry analysis, was confirmed to be Musa acuminata ssp. malaccensis. Using a self-derived F₂ population segregating for STR4 resistance, quantitative trait loci sequencing (QTL-seq) was performed on bulks consisting of resistant and susceptible individuals. Changes in SNP index between the bulks revealed a major QTL located on the distal end of the long arm of chromosome 3. Multiple resistance genes are present in this region. Identification of chromosome regions conferring resistance to Foc can facilitate marker assisted selection in breeding programs and paves the way towards identifying genes underpinning resistance.

The microbial communities that inhabit the intestinal tract play an important role in modulating health and productivity. Environmental stressors can impact microbial communities, which can significantly influence host physiology. Cattle are subjected to several environmental stressors when placed on feedlots, such as transportation stress, exposure to feedlot environments and change in diet and management. Exposure to these stressors could influence host gut microbiota, which in turn, could potentially influence host health and performance. The aim of the current study was to characterise the temporal changes that occur in intestinal microbiota as a consequence of feedlot placement by profiling 16s rRNA sequences in rectal faecal samples. When faecal microbiome profiles were compared in terms of relative abundances and alpha diversity metrics, the results showed significant, observable changes in profiles 2 days post-feedlot induction. Furthermore, beta-diversity analysis indicated that the phylogenetic similarity between samples significantly decreased on day 2 (PERMANOVA, p < 0.001). These trends were suggestive of a short-term reduction in microbial diversity coupled with decreased similarity between animals. These changes warrant further investigation and could provide opportunities for improved performance, health and even welfare of feedlot cattle in future.

SUMMARY: Progesterone receptor membrane component 1 (PGRMC1) is often elevated in cancers, and exists in alternative states of phosphorylation. A motif centered on PGRMC1 Y180 was evolutionarily acquired concurrently with the embryological gastrulation organizer that orchestrates vertebrate tissue differentiation. Here, we show that mutagenic manipulation of PGRMC1 phosphorylation alters cell metabolism, genomic stability, and CpG methylation. Each of several mutants elicited distinct patterns of genomic CpG methylation. Mutation of S57A/Y180/S181A led to increased net hypermethylation, reminiscent of embryonic stem cells. Pathways enrichment analysis suggested modulation of processes related to animal cell differentiation status and tissue identity, as well as cell cycle control and ATM/ATR DNA damage repair regulation. We detected different genomic mutation rates in culture. A companion manuscript shows that these cell states dramatically affect protein abundances, cell and mitochondrial morphology, and glycolytic metabolism. We propose that PGRMC1 phosphorylation status modulates cellular plasticity mechanisms relevant to early embryological tissue differentiation.

Poxvirus systems have been extensively used as vaccine vectors. Herein a systems vaccinology analysis of intramuscular injection sites provides detailed insights into host innate immune responses, as well as expression of vector and recombinant immunogen genes, after vaccination with a new multiplication defective, vaccinia-based vector, Sementis Copenhagen Vector. Chikungunya and Zika virus immunogen mRNA and protein expression was associated with necrosing skeletal muscle cells surrounded by mixed cellular infiltrates. Adjuvant signatures at 12 hours post-vaccination were dominated by TLR3, 4 and 9, STING, MAVS, PKR and the inflammasome. Th1 cytokine signatures were dominated by IFNγ, TNF and IL1β, and chemokine signatures by CCL5 and CXCL12. Multiple signatures associated with dendritic cell stimulation were evident. By day seven, vaccine transcripts were absent, and cell death, neutrophil, macrophage and inflammation annotations had abated. No compelling arthritis signatures were identified. Such innate systems vaccinology approaches should inform refinements in poxvirus-based vector design.

Health services are rapidly adopting digital systems, but health data remain unstandardised and segregated across separate healthcare providers. Allergy serves as a universally important use case since type I mediated reactions to medications, foods and environmental substances, impact a plethora of health services. Australia has among the highest rates of allergic diseases globally, with 30% of the population affected, costing $A18.9b and $A44.6b in health and non-financial impacts annually. A Commonwealth Parliamentary Inquiry into Allergy and Anaphylaxis (2020) delivered 24 recommendations that underpinned foundation of the National Allergy Council and National Allergy Centre of Excellence (2022). While our National Digital Health Strategy (2023–2028) guides integration of primary and tertiary health data for clinical decision support, secure health data access for research needs prioritisation. Here we consolidate regulatory, ethical, privacy and technical considerations for accessing, integrating and analysing health data for generation of new insights to inform health system improvement. We found through document tracking and sector knowledge as many as 77 national level documents relating to legislation, policy, strategy, roadmaps, standards, frameworks, guidelines and infrastructure, from 24 different national agencies linked to seven federal government departments. This perspective on the complex national landscape of digital health regulation identifies the challenges and suggests a GATEway framework to navigate fragmented health data, distributed responsibilities, and requirements of multiple stakeholders involved in guiding and governing ethical and secure access to large-scale health data assets for research analyses. With increasing allergy prevalence, expediting digital health analytical capabilities is a critical priority to drive evidence-based improvements in allergy care.