Transcriptomic response and immunological responses to chimpanzee adenovirus- and MVA viral-vectored vaccines for RSV in healthy adults.

Cohorts of healthy younger adults (18-50yrs) and healthy older adults (60-75yrs) were immunized intramuscularly or intranasally with an adenovirus-vectored RSV vaccine (PanAd3-RSV) as a prime dose and boosted with PanAd3-RSV or a poxvirus-vectored vaccine (MVA-RSV) encoding the same insert. Whole blood gene expression was measured at baseline, 3- and 7-days post vaccination. Intramuscular prime vaccination with PanAd3-RSV induced differential expression of 643 genes (DEGs, FDR < 0.05). Intranasal prime vaccination with PanAd3-RSV did not induce any differentially expressed genes (DEGs) in blood samples at 3 days post vaccination. Intranasally primed participants showed greater numbers of DEGS on boosting than intramuscularly primed participants. The most highly enriched biological processes related to DEGs after both prime and boost vaccination were type-1 interferon related pathways, lymphocytic and humoral immune responses.

IFITM3 restricts virus-induced inflammatory cytokine production by limiting Nogo-B mediated TLR responses.

Interferon-induced transmembrane protein 3 (IFITM3) is a restriction factor that limits viral pathogenesis and exerts poorly understood immunoregulatory functions. Here, using human and mouse models, we demonstrate that IFITM3 promotes MyD88-dependent, TLR-mediated IL-6 production following exposure to cytomegalovirus (CMV). IFITM3 also restricts IL-6 production in response to influenza and SARS-CoV-2. In dendritic cells, IFITM3 binds to the reticulon 4 isoform Nogo-B and promotes its proteasomal degradation. We reveal that Nogo-B mediates TLR-dependent pro-inflammatory cytokine production and promotes viral pathogenesis in vivo, and in the case of TLR2 responses, this process involves alteration of TLR2 cellular localization. Nogo-B deletion abrogates inflammatory cytokine responses and associated disease in virus-infected IFITM3-deficient mice. Thus, we uncover Nogo-B as a driver of viral pathogenesis and highlight an immunoregulatory pathway in which IFITM3 fine-tunes the responsiveness of myeloid cells to viral stimulation.

Parental TB associated with offspring asthma and rhinitis.

BACKGROUND: Infections in early life are associated with asthma and allergies in one-generation settings; however, the link between parental infection and offspring phenotype is rarely investigated. We aim to study the association of parental TB before conception of the offspring with offspring asthma and rhinitis.METHODS: We included 2,965 offspring born in 1985-2004 and registered in the Norwegian prescription database to 1,790 parents born after 1960 with a history of TB, and included in the Norwegian TB registry. Offspring asthma (n = 582) and rhinitis (n = 929) were defined based on diagnosis, type of medication and prescribed medication ≥1 year. Associations of parental TB <8 years, ≥8 years but before offspring´s birth year and after birth (reference category) with offspring asthma and rhinitis were analysed using logistic regression.RESULTS: Asthma risk was higher in persons with parental TB in childhood (OR 1.73, 95% CI 1.20-2.50) or later preconception (OR 1.38, 95% CI 1.00-1.91) than in persons with parental TB after offspring´s birth; this was significant only in the maternal line (childhood: OR 1.95, 95% CI 1.13-3.37; later preconception: OR 1.74, 95% CI 1.08-2.80). Associations with rhinitis were not identified.CONCLUSIONS: Parental childhood TB was associated with higher asthma risk in future offspring. We speculate that TB impacts maternal immunity and dysregulates the offspring´s type 2 immunity, and that TB-induced epigenetic reprograming of immune defences are transferred to the offspring.

Morphological variation in the horse: defining complex traits of body size and shape.

Horses, like many domesticated species, have been selected for broad variation in skeletal size. This variation is not only an interesting model of rapid evolutionary change during domestication, but is also directly applicable to the horse industry. Breeders select for complex traits like body size and skeletal conformation to improve marketability, function, soundness and performance in the show ring. Using a well-defined set of 35 measurements, we have identified and quantified skeletal variation in the horse species. We collected measurements from 1215 horses representing 65 breeds of diverse conformation such as the American Miniature, Shetland Pony, Arabian Horse, Thoroughbred, Shire and Clydesdale. Principal components analysis has identified two key dimensions of skeletal variation in the horse. Principal component 1 is positively correlated with every measurement and quantifies overall body size. Principal component 2 captures a pattern of bone widths vs. lengths and thus quantifies variation in overall bone thickness. By defining these complex skeletal traits, we have created a framework for whole genome association studies to identify quantitative trait loci that contribute to this variation.