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Klebsiella pneumoniae is a leading cause of hospital-acquired infections as well as the leading cause of neonatal sepsis worldwide. Further, increasing antibiotic resistance in this pathogen makes K. pneumoniae troublesome to treat. Despite its clinical importance, there is not yet an approved K. pneumoniae vaccine available. Here we tested antibody durability and long-term functionality of two previously reported bioconjugate vaccines targeting the K. pneumoniae capsular type K2 and O-antigen type O1v1. We demonstrate that both antibodies are durable in mice for up to six months with significant IgG titers. However, only the K2 antibodies exhibit functionality out to six months as evidenced by serum bactericidal activity and survival in a murine bacteremia challenge model. These results are another promising step towards demonstrating the clinical capacity of bioconjugate vaccines and their induction of durable antibody responses., Competing Interests: Declaration of competing interest CJK and CMH have a financial stake in Omniose, a for-profit entity developing bioconjugate vaccines using patented technology derived from the data presented in this and other published manuscripts. PLW, ECM, and DAR have no conflicts to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Klebsiella pneumoniae causes community- and healthcare-associated infections in children and adults. Globally in 2019, an estimated 1.27 million (95% Uncertainty Interval [UI]: 0.91-1.71) and 4.95 million (95% UI: 3.62-6.57) deaths were attributed to and associated with bacterial antimicrobial resistance (AMR), respectively. K. pneumoniae was the second leading pathogen in deaths attributed to AMR resistant bacteria. Furthermore, the rise of antimicrobial resistance in both community- and hospital-acquired infections is a concern for neonates and infants who are at high risk for invasive bacterial disease. There is a limited antibiotic pipeline for new antibiotics to treat multidrug resistant infections, and vaccines targeted against K. pneumoniae are considered to be of priority by the World Health Organization. Vaccination of pregnant women against K. pneumoniae could reduce the risk of invasive K.pneumoniae disease in their young offspring. In addition, vulnerable children, adolescents and adult populations at risk of K. pneumoniae disease with underlying diseases such as immunosuppression from underlying hematologic malignancy, chemotherapy, patients undergoing abdominal and/or urinary surgical procedures, or prolonged intensive care management are also potential target groups for a K. pneumoniae vaccine. A 'Vaccine Value Profile' (VVP) for K.pneumoniae, which contemplates vaccination of pregnant women to protect their babies from birth through to at least three months of age and other high-risk populations, provides a high-level, holistic assessment of the available information to inform the potential public health, economic and societal value of a pipeline of K. pneumoniae vaccines and other preventatives and therapeutics. This VVP was developed by a working group of subject matter experts from academia, non-profit organizations, public-private partnerships, and multi-lateral organizations, and in collaboration with stakeholders from the WHO. All contributors have extensive expertise on various elements of the K.pneumoniae VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ziyaad Dangor reports financial support was provided by Bill & Melinda Gates Foundation. Ziyaad Dangor reports financial support was provided by World Health Organization. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Gene expression profiles are increasingly being used as biomarkers to detect the physiological responses of a number of species to disease, nutrition, and other stressors. However, little attention has been given to using gene expression to assess the stressors and physiological status of marine mammals. We sought to develop and validate a nutrigenomic approach to quantify nutritional stress in Steller sea lions (Eumetopias jubatus). We subjected 4 female Steller sea lions to 3 feeding regimes over 70-day trials (unrestricted food intake, acute nutritional stress, and chronic nutritional stress), and drew blood samples from each animal at the end of each feeding regime. We then extracted the RNA of white blood cells and measured the response of 8 genes known to react to diet restriction in terrestrial mammals. Overall, we found that the genomic response of Steller sea lions experiencing nutritional stress was consistent with how terrestrial mammals respond to dietary restrictions. Our nutritionally stressed sea lions down-regulated some cellular processes involved in immune response and oxidative stress, and up-regulated pro-inflammatory responses and metabolic processes. Nutrigenomics appears to be a promising means to monitor nutritional status and contribute to mitigation measures needed to assist in the recovery of Steller sea lions and other at-risk species of marine mammals., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Physiological responses to changes in energy balance are tightly regulated by the endocrine system through glucocorticoids, IGF-I and thyroid hormones. Changes in these hormones were studied in eight captive female Steller sea lions that experienced changes in food intake, body mass, body composition, and blood metabolites during summer and winter. During a period of energy restriction, one group of sea lions was fed reduced amounts of Pacific herring and another was fed an isocaloric diet of walleye pollock, after which both groups returned to their pre-experimental diets of herring. Cortisol was negatively and IGF-I was positively associated with changes in body mass during periods of energy restriction (mass loss associated with increase in cortisol and decrease in IGF-I) and refeeding (body mass maintenance associated with stable hormone concentrations in summer and compensatory growth linked to decrease in cortisol and increase in IGF-I in winter). Cortisol and IGF-I were also correlated with changes in lipid and lean mass, respectively. Consequently, these two hormones likely make adequate biomarkers for nutritional stress in sea lions, and when combined provide indication of the energetic strategy (lipid vs lean mass catabolism) animals adopt to cope with changes in nutrient intake. Unlike type of diet fed to the sea lions, age of the animals also impacted hormonal responses, with younger animals showing more intense hormonal changes to nutritional stress. Thyroid hormones, however, were not linked to any physiological changes observed in this study.

The heat increment of feeding (HIF) was measured in six captive, juvenile Steller sea lions (Eumetopias jubatus), fed meals of either 2 or 4 kg of herring. HIF was calculated as the post-prandial increase in metabolism above baseline levels, and was measured using open-circuit (gas) respirometry. It averaged 12.4 +/- 0.9% (SE) of ingested energy intake for the 4-kg meal trials, and 9.9 +/- 0.9% for the 2-kg meal size. The effect lasted 8-10 hr for the larger meal size. Metabolism peaked 3.7 hr after feeding, and was 2.13 times higher than baseline levels. For the 2-kg meal size, the effect lasted 6-8 hr, with metabolism peaking 2.8 hr after ingestion at 1.76 times baseline levels. Our estimates of HIF for Steller sea lions are at the lower end of estimates for terrestrial mammals, and are consistent with estimates for other marine mammals.

Two patients had uniocular visual loss after methylprednisolone acetate (Depo-Medrol) injection for control of chronic inflammatory conditions in the nose. The cause of the visual loss was embolic retinal and choroidal vascular occlusion. The emboli were presumably aggregates of microcrystals of methylprednisolone acetate.