Impact of Th1 CD4 Follicular Helper T Cell Skewing on Antibody Responses to an HIV-1 Vaccine in Rhesus Macaques.

Generating durable humoral immunity through vaccination depends upon effective interactions of follicular helper T (Tfh) cells with germinal center (GC) B cells. Th1 polarization of Tfh cells is an important process shaping the success of Tfh-GC B cell interactions by influencing costimulatory and cytokine-dependent Tfh help to B cells. However, the question remains as to whether adjuvant-dependent modulation of Tfh cells enhances HIV-1 vaccine-induced antienvelope (anti-Env) antibody responses. We investigated whether an HIV-1 vaccine platform designed to increase the number of Th1-polarized Tfh cells enhances the magnitude and quality of anti-Env antibodies. Utilizing a novel interferon-induced protein 10 (IP-10)-adjuvanted HIV-1 DNA prime followed by a monophosphoryl lipid A and QS-21 (MPLA+QS-21)-adjuvanted Env protein boost (DIP-10 PALFQ) in macaques, we observed higher anti-Env serum IgG titers with greater cross-clade reactivity, specificity for V1V2, and effector functions than in macaques primed with DNA lacking IP-10 and boosted with MPLA-plus-alum-adjuvanted Env protein (DPALFA) The DIP-10 PALFQ vaccine regimen elicited higher anti-Env IgG1 and lower IgG4 antibody levels in serum, showing for the first time that adjuvants can dramatically impact the IgG subclass profile in macaques. The DIP-10 PALFQ regimen also increased vaginal and rectal IgA antibodies to a greater extent. Within lymph nodes, we observed augmented GC B cell responses and the promotion of Th1 gene expression profiles in GC Tfh cells. The frequency of GC Tfh cells correlated with both the magnitude and avidity of anti-Env serum IgG. Together, these data suggest that adjuvant-induced stimulation of Th1-Tfh cells is an effective strategy for enhancing the magnitude and quality of anti-Env antibody responses.IMPORTANCE The results of the RV144 trial demonstrated that vaccination could prevent HIV transmission in humans and that longevity of anti-Env antibodies may be key to this protection. Efforts to improve upon the prime-boost vaccine regimen used in RV144 have indicated that booster immunizations can increase serum anti-Env antibody titers but only transiently. Poor antibody durability hampers efforts to develop an effective HIV-1 vaccine. This study was designed to identify the specific elements involved in the immunological mechanism necessary to produce robust HIV-1-specific antibodies in rhesus macaques. By clearly defining immune-mediated pathways that improve the magnitude and functionality of the anti-HIV-1 antibody response, we will have the foundation necessary for the rational development of an HIV-1 vaccine

Adaptation and transformation

Transformation as an adaptive response to climate change opens a range of novel policy options. Used to describe responses that produce non-linear changes in systems or their host social and ecological environments, transformation also raises distinct ethical and procedural questions for decision-makers. Expanding adaptation to include transformation foregrounds questions of power and preference that have so far been underdeveloped in adaptation theory and practice. We build on David Harvey’s notion of activity space to derive a framework and research agenda for climate change adaptation seen as a political decisionpoint and as an opportunity for transformation, incremental adjustment or resistance to change in development pathway. Decision-making is unpacked through the notion of the activity space into seven coevolving sites: the individual, technology, livelihoods, discourse, behaviour, the environment and institutions. The framework is tested against practitioner priorities to define an agenda that can make coherent advances in research and practice on climate change adaptation

Positioning resilience for 2015: The role of resistance, incremental adjustment and transformation in disaster risk management policy

Resilience is a ubiquitous term in disaster ris

Positioning resilience for 2015: The role of resistance, incremental adjustment and transformation in disaster risk management policy

Resilience is a ubiquitous term in disaster ris

CD8+ and CD8- NKT cells exhibit phenotypic changes during pregnancy

Background: NKT cell population is a relatively well-characterized immune cell subset. Numerous publications have characterized the phenotypical features of its subpopulations even in human pregnancy. Nevertheless, there have not been studies investigating the distribution of the NKT cells based on the surface presence of the CD8 receptor. Methods: Thirty-four pregnant women from the first trimester, 30 from the second, and 36 from the third trimester of pregnancy in addition to 35 healthy non-pregnant women have been involved in the study. PBMCs were isolated from peripheral blood, CD8+ and CD8- NKT cells were then studied by flow cytometry using monoclonal antibodies. Immune checkpoint molecules and intracellular markers were also measured. Results: Substantial differences were revealed in the proportions of the NKT cell subpopulations in the healthy control cohort and the pregnant groups. By comparing the investigated groups, significant changes were detected in the expression levels of PD-L1, TIGIT, CD155, and NKG2D. Further associations were observed through examination of the relative expressions of TIGIT and CD226 in the CD8+ NKT subset. Conclusion: Data suggest that the CD8+ NKT cells are under fine regulation during healthy human pregnancy

Enabling strategies and impeding factors to urban resilience implementation : a scoping review

Despite growing interest in urban resilience, there is a significant gap between discourse and the capacity to develop resilience in practice. This scoping review assembles and shares evidence and insights from empirical studies of attempts to implement urban resilience published between 2005 and 2017. More precisely, it seeks to identify enabling strategies, impeding factors and trade‐offs in the implementation of urban resilience. Findings are presented along the dimensions of urban resilience detailed in the City Resilience Framework (ARUP/Rockefeller Foundation): Health and Wellbeing, Economy and Society, Infrastructure and Environment, and Leadership and Strategy (which we present as a cross‐cutting theme). While some enabling and impeding factors in implementation are associated with a specific dimension, others are common to all three. Across dimensions, we find that transparent, inclusive and supportive governance reduces the risk of negative impact that resilience implementation will have on communities. Conflicting priorities of managing risk and meeting short‐term needs are found to diminish the potential for transformative resilience action. Integrating risk into planning appears as a promising strategy in all dimensions of resilience. Trade‐offs are found in resilience implementation, and range from adverse effects associated with infrastructure to power imbalances when the power to implement resilience privileges one system level over another

Can there be calm during a cytokine storm? : immune checkpoint pathways affecting the severity of COVID-19 disease

Introduction: The COVID-19 pandemic has become a global health crisis, eliciting varying severity in infected individuals. This study aimed to explore the immune profiles between moderate and severe COVID-19 patients experiencing a cytokine storm and their association with mortality. This study highlights the role of PD-1/PD-L1 and the TIGIT/CD226/CD155/CD112 pathways in COVID-19 patients. Methods: We performed a study using flow cytometry to compare the phenotypic and functional characteristics of peripheral blood mononuclear cells in patients with moderate or severe disease and healthy individuals. Soluble immune checkpoint molecule and ligand levels were measured by Luminex. Results: Severe patients show reduced CD8+ T cell frequency, hyperactivation of CD8+ T, NK and NKT cells with concurrent upregulation of immune checkpoint ligands in monocytes. TIGIT expression by CD8+ T and NK cells and PD-1 by NKT cells suggest a spectrum of immune dysfunction, encompassing both hyperactivation and features of exhaustion. This dual phenomenon likely contributes to the impaired viral clearance and the exacerbation of inflammation characteristic of severe disease. Additionally, the study suggests that increased activation and cytotoxicity of NK cells may be associated with fatal outcomes in severe COVID-19 infection. Conclusion: These findings shed light on the intricate immune response regulation in COVID-19, emphasizing the importance of immune checkpoint pathways and activation signatures in disease severity. A novel aspect of this study is that it includes only COVID-19 patients experiencing cytokine storms, allowing for a focused analysis of immune dysregulation during this critical phase of the disease

A Novel Low-Cost, Recyclable, Easy-to-Build Robot Blimp For Transporting Supplies in Hard-to-Reach Locations

Rural communities in remote areas often encounter significant challenges when it comes to accessing emergency healthcare services and essential supplies due to a lack of adequate transportation infrastructure. The situation is further exacerbated by poorly maintained, damaged, or flooded roads, making it arduous for rural residents to obtain the necessary aid in critical situations. Limited budgets and technological constraints pose additional obstacles, hindering the prompt response of local rescue teams during emergencies. The transportation of crucial resources, such as medical supplies and food, plays a vital role in saving lives in these situations. In light of these obstacles, our objective is to improve accessibility and alleviate the suffering of vulnerable populations by automating transportation tasks using low-cost robotic systems. We propose a low-cost, easy-to-build blimp robot (UAVs), that can significantly enhance the efficiency and effectiveness of local emergency responses.Comment: IEEE Global Humanitarian Technology Conference (GHTC 2023

Immune checkpoint receptor expression profiles of MAIT cells in moderate and severe COVID-19

MAIT cells are one of the largest unconventional T cell populations and, recruited to the site of infection, play both protective and pathogenic roles during pulmonary viral infections. MAIT cell activation patterns change significantly during COVID-19, with a notable decrease in their frequency in peripheral blood of severe cases. In the present study, we aimed to investigate the expression profiles of various immune checkpoint pathways on MAIT, MAIT-like and non-MAIT cells in moderate and severe COVID-19 patients undergoing cytokine storm. Despite numerous studies comparing MAIT cell characteristics based on COVID-19 disease severity, none have delved into the critical differences in MAIT cell immune checkpoint profiles between moderate and severe COVID-19 patients, all experiencing a cytokine storm. Flow cytometry was used to analyse peripheral blood mononuclear cells from a cohort of 35 patients, comprising 18 moderate and 17 severe cases, alongside 14 healthy controls. Our investigation specifically focuses on severe COVID-19 presentations, revealing a marked deletion of MAIT cells. Further exploration into the regulatory dynamics of MAIT cell functionality reveals shifts in the expression profiles of critical immune checkpoint receptors, notably PD-1 and CD226. In severe COVID-19 patients, MAIT cells showed a significant decrease in the expression of CD226, whereas MAIT-like and non-MAIT cells demonstrated a significant increase in the expression of PD-1 compared to healthy individuals. The expression of the TIGIT receptor remained unaltered across all investigated groups. Our findings contribute to the existing knowledge by elucidating the changes in MAIT cell subpopulations and their potential role in COVID-19 disease severity