A Liposome-Based Mycobacterial Vaccine Induces Potent Adult and Neonatal Multifunctional T Cells through the Exquisite Targeting of Dendritic Cells

BACKGROUND: In the search for more potent and safer tuberculosis vaccines, CAF01 was identified as a remarkable formulation. Based on cationic liposomes and including a synthetic mycobacterial glycolipid as TLR-independent immunomodulator, it induces strong and protective T helper-1 and T helper-17 adult murine responses to Ag85B-ESAT-6, a major mycobacterial fusion protein. Here, we assessed whether these properties extend to early life and how CAF01 mediates its adjuvant properties in vivo. METHODS/FINDINGS: Following adult or neonatal murine immunization, Ag85B-ESAT-6/CAF01 similarly reduced the post-challenge bacterial growth of M. bovis BCG, whereas no protection was observed using Alum as control. This protection was mediated by the induction of similarly strong Th1 and Th17 responses in both age groups. Multifunctional Th1 cells were already elicited after a single vaccine dose and persisted at high levels for at least 6 months even after neonatal priming. Unexpectedly, this potent adjuvanticity was not mediated by a massive targeting/activation of dendritic cells: in contrast, very few DCs in the draining lymph nodes were bearing the labeled antigen/adjuvant. The increased expression of the CD40 and CD86 activation markers was restricted to the minute portion of adjuvant-bearing DCs. However, vaccine-associated activated DCs were recovered several days after immunization. CONCLUSION: The potent adult and neonatal adjuvanticity of CAF01 is associated in vivo with an exquisite but prolonged DC uptake and activation, fulfilling the preclinical requirements for novel tuberculosis vaccines to be used in early life

Cationic Liposomes Formulated with Synthetic Mycobacterial Cordfactor (CAF01): A Versatile Adjuvant for Vaccines with Different Immunological Requirements

It is now emerging that for vaccines against a range of diseases including influenza, malaria and HIV, the induction of a humoral response is insufficient and a substantial complementary cell-mediated immune response is necessary for adequate protection. Furthermore, for some diseases such as tuberculosis, a cellular response seems to be the sole effector mechanism required for protection. The development of new adjuvants capable of inducing highly complex immune responses with strong antigen-specific T-cell responses in addition to antibodies is therefore urgently needed. (cell-mediated/humoral) and malaria (humoral) immunization with CAF01-based vaccines elicited significant protective immunity against challenge.CAF01 is potentially a suitable adjuvant for a wide range of diseases including targets requiring both CMI and humoral immune responses for protection

Hydroclimatic Controls on the Isotopic (δ18 O, δ2 H, d-excess) Traits of Pan-Arctic Summer Rainfall Events

Arctic sea-ice loss is emblematic of an amplified Arctic water cycle and has critical feedback implications for global climate. Stable isotopes (δ18O, δ2H, d-excess) are valuable tracers for constraining water cycle and climate processes through space and time. Yet, the paucity of well-resolved Arctic isotope data preclude an empirically derived understanding of the hydrologic changes occurring today, in the deep (geologic) past, and in the future. To address this knowledge gap, the Pan-Arctic Precipitation Isotope Network (PAPIN) was established in 2018 to coordinate precipitation sampling at 19 stations across key tundra, subarctic, maritime, and continental climate zones. Here, we present a first assessment of rainfall samples collected in summer 2018 (n = 281) and combine new isotope and meteorological data with sea ice observations, reanalysis data, and model simulations. Data collectively establish a summer Arctic Meteoric Water Line where δ2H = 7.6⋅δ18O–1.8 (r2 = 0.96, p < 0.01). Mean amount-weighted δ18O, δ2H, and d-excess values were −12.3, −93.5, and 4.9‰, respectively, with the lowest summer mean δ18O value observed in northwest Greenland (−19.9‰) and the highest in Iceland (−7.3‰). Southern Alaska recorded the lowest mean d-excess (−8.2%) and northern Russia the highest (9.9‰). We identify a range of δ18O-temperature coefficients from 0.31‰/°C (Alaska) to 0.93‰/°C (Russia). The steepest regression slopes (>0.75‰/°C) were observed at continental sites, while statistically significant temperature relations were generally absent at coastal stations. Model outputs indicate that 68% of the summer precipitating air masses were transported into the Arctic from mid-latitudes and were characterized by relatively high δ18O values. Yet 32% of precipitation events, characterized by lower δ18O and high d-excess values, derived from northerly air masses transported from the Arctic Ocean and/or its marginal seas, highlighting key emergent oceanic moisture sources as sea ice cover declines. Resolving these processes across broader spatial-temporal scales is an ongoing research priority, and will be key to quantifying the past, present, and future feedbacks of an amplified Arctic water cycle on the global climate system. © Copyright © 2021 Mellat, Bailey, Mustonen, Marttila, Klein, Gribanov, Bret-Harte, Chupakov, Divine, Else, Filippov, Hyöky, Jones, Kirpotin, Kroon, Markussen, Nielsen, Olsen, Paavola, Pokrovsky, Prokushkin, Rasch, Raundrup, Suominen, Syvänperä, Vignisson, Zarov and Welker.We gratefully acknowledge all participating PAPIN stations. Tarja T?rm?nen and Aino Erkinaro assisted with sample analysis at the Stable Isotope Laboratory, University of Oulu. Shawn Marriott, Patrick Duke and Polar Knowledge Canada are acknowledged for their support with the Canadian High Arctic Research Station. Sergey Serikov and Aleksandr Sokolov assisted with Russian precipitation sampling. The NOAA Air Resources Laboratory (ARL) is gratefully acknowledged for provision of the HYSPLIT transport model used in this study. NCEP/NCAR data were obtained from the National Oceanic and Atmospheric Administration (NOAA) Earth System Research Laboratory?s (ESRL) Physical Sciences Laboratory database. Funding. The Pan-Arctic Precipitation Isotope Network (PAPIN) received funding from the European Union?s Horizon 2020 Project INTERACT, under Grant Agreement No.730938 (JW PI). An Academy of Finland Grant (316014-JW PI). Support was also provided by a University of the Arctic Research Chairship to JW that funded isotope analyses and provided postdoctoral support for HB and K-RM and postgraduate research support for MM. A Russian Science Foundation Grant (No. 18-11-00024) to KG funded isotope analyses. SK was thankful to Russian Science Foundation (No. 20-67-46018). Russian Foundation for Basic Research (BFBR) supported isotopic analyses conducted by AP (#18-05-60203-Arktika)

Pregnant Behind Bars: Meeting the Nutrition Needs of Incarcerated Pregnant Women

The number of women involved in the criminal justice system has increased dramatically over the past 20 years. Due to their marginalized background, incarcerated women have a complex set of health-related needs. This is especially true of those who are pregnant, a particularly vulnerable, high-risk group. Although guidelines have been developed that recommend pregnancy screening, provision of dietary supplements, regular nutritious meals, and nutritional counseling for incarcerated pregnant women, jail policies and health care protocols often fail to heed these recommendations. In this chapter, we discuss the nutritional needs of pregnant incarcerated women as well as breastfeeding in the context of the criminal justice system and consider some of the challenges in developing programming and policies to address these health-related needs. We also present findings from the William & Mary Healthy Beginnings Project, a nutrition intervention program developed for pregnant incarcerated women in Southeastern Virginia. Assessment of this program suggests that through the development of protocols and polices that consider the health-related needs of pregnant women, correctional facilities could play a pivotal role in helping incarcerated women develop healthier habits to better care for themselves and their newborns.https://scholarworks.wm.edu/asbookchapters/1106/thumbnail.jp

Hydroclimatic Controls on the Isotopic (δ18 O, δ2 H, d-excess) Traits of Pan-Arctic Summer Rainfall Events

Arctic sea-ice loss is emblematic of an amplified Arctic water cycle and has critical feedback implications for global climate. Stable isotopes (delta O-18, delta H-2, d-excess) are valuable tracers for constraining water cycle and climate processes through space and time. Yet, the paucity of well-resolved Arctic isotope data preclude an empirically derived understanding of the hydrologic changes occurring today, in the deep (geologic) past, and in the future. To address this knowledge gap, the Pan-Arctic Precipitation Isotope Network (PAPIN) was established in 2018 to coordinate precipitation sampling at 19 stations across key tundra, subarctic, maritime, and continental climate zones. Here, we present a first assessment of rainfall samples collected in summer 2018 (n = 281) and combine new isotope and meteorological data with sea ice observations, reanalysis data, and model simulations. Data collectively establish a summer Arctic Meteoric Water Line where delta H-2 = 7.6.delta O-18-1.8 (r(2) = 0.96, p 0.75 parts per thousand/degrees C) were observed at continental sites, while statistically significant temperature relations were generally absent at coastal stations. Model outputs indicate that 68% of the summer precipitating air masses were transported into the Arctic from mid-latitudes and were characterized by relatively high delta O-18 values. Yet 32% of precipitation events, characterized by lower delta O-18 and high d-excess values, derived from northerly air masses transported from the Arctic Ocean and/or its marginal seas, highlighting key emergent oceanic moisture sources as sea ice cover declines. Resolving these processes across broader spatial-temporal scales is an ongoing research priority, and will be key to quantifying the past, present, and future feedbacks of an amplified Arctic water cycle on the global climate system

Åpen form – en utvidet utøverrolle

Artistic research "OPEN FORM - An Expanded Performer´s Role" is available at: OPEN FORM - An Expanded Performer´s Role. Else Olsen S, The Grieg Academy, University of Bergen, Norway</a