Investment case for eliminating mother-to-child transmission of syphilis: promoting better maternal and child health and stronger health systems

Mother-to-child transmission (MTCT) of syphilis (commonly referred to as “congenital syphilis”) is relatively simple to eliminate and it is inexpensive to detect and treat, making it a possible “easy win” in terms of cost, feasibility and speed of scale-up. Investing in screening and treatment for syphilis in pregnant women ranks as one of the most cost-effective antenatal interventions. Screening all pregnant women, using simple and low-cost technologies, is feasible, even in low-resource settings. Syphilis is easily cured with penicillin, and MTCT of syphilis is easily prevented when pregnant mothers with syphilis infection are identified early and treated promptly. Penicillin is off patent, widely available, on the World Health Organization (WHO) list of essential medicines and, above all, inexpensive

T-cell dependent immunogenicity of protein therapeutics: Preclinical assessment and mitigation

Protein therapeutics hold a prominent and rapidly expanding place among medicinal products. Purified blood products, recombinant cytokines, growth factors, enzyme replacement factors, monoclonal antibodies, fusion proteins, and chimeric fusion proteins are all examples of therapeutic proteins that have been developed in the past few decades and approved for use in the treatment of human disease. Despite early belief that the fully human nature of these proteins would represent a significant advantage, adverse effects associated with immune responses to some biologic therapies have become a topic of some concern. As a result, drug developers are devising strategies to assess immune responses to protein therapeutics during both the preclinical and the clinical phases of development. While there are many factors that contribute to protein immunogenicity, T cell- (thymus-) dependent (Td) responses appear to play a critical role in the development of antibody responses to biologic therapeutics. A range of methodologies to predict and measure Td immune responses to protein drugs has been developed. This review will focus on the Td contribution to immunogenicity, summarizing current approaches for the prediction and measurement of T cell-dependent immune responses to protein biologics, discussing the advantages and limitations of these technologies, and suggesting a practical approach for assessing and mitigating Td immunogenicity

Transcriptional response of ovine lung to infection with jaagsiekte sheep retrovirus

Jaagsiekte sheep retrovirus (JSRV) is the etiologic agent of ovine pulmonary adenocarcinoma (OPA), a neoplastic lung disease of sheep. OPA is an important economic and welfare issue for sheep farmers and a valuable naturally-occurring animal model for human lung adenocarcinoma. Here, we used RNA sequencing to study the transcriptional response of ovine lung tissue to infection by JSRV. We identified 1,971 ovine genes differentially-expressed in JSRV-infected lung compared to non-infected lung, including many genes with roles in carcinogenesis and immunomodulation. The differential expression of selected genes was confirmed using immunohistochemistry and RT-qPCR. A key finding was the activation of anterior-gradient-2, yes-associated protein-1 and amphiregulin in OPA tumor cells, indicating a role for this oncogenic pathway in OPA. In addition, there was differential expression of genes related to innate immunity including genes encoding cytokines, chemokines and complement system proteins. In contrast, there was little evidence for upregulation of genes involved in T-cell immunity. Many genes related to macrophage function were also differentially expressed, reflecting the increased abundance of these cells in OPA-affected lung tissue. Comparison of the genes differentially regulated in OPA with transcriptional changes occurring in human lung cancer revealed important similarities and differences between OPA and human lung adenocarcinoma. This study provides valuable new information on the pathogenesis of OPA and strengthens the use of this naturally occurring animal model for human lung adenocarcinoma

Application of IgG-Derived Natural Treg Epitopes (IgG Tregitopes) to Antigen-Specific Tolerance Induction in a Murine Model of Type 1 Diabetes

HLA class II-restricted regulatory T cell (Treg) epitopes in IgG (also called “Tregitopes”) have been reported to suppress immune responses to coadministered antigens by stimulating the expansion of natural Tregs (nTregs). Here we evaluate their impact on human immune responses to islet cell antigens ex vivo and on the modulation of type 1 diabetes (T1D) in a murine model in vivo. Co-administration of Tregitopes and T1D antigens delayed development of hyperglycemia and reduced the incidence of diabetes in NOD mice. Suppression of diabetes could be observed even following onset of disease. To measure the impact of Tregitope treatment on T cell responses, we evaluated the effect of Tregitope treatment in DO11.10 mice. Upregulation of FoxP3 in KJ1-26-stained OVA-specific CD4+ T cells was observed following treatment of DO11.10 mice with Tregitopes, along with reductions in anti-OVA Ig and T effector responses. In ex vivo studies of human T cells, peripheral blood mononuclear cells’ (PBMC) responses to GAD65 epitopes in the presence and absence of Tregitope were variable. Suppression of immune responses to GAD65 epitopes ex vivo by Tregitope appeared to be more effective in assays using PBMC from a newly diagnosed diabetic subject than for other more established diabetic subjects, and correlation of the degree of suppression with predicted HLA restriction of the Tregitopes was confirmed. Implementation of these defined regulatory T cell epitopes for therapy of T1D and other autoimmune diseases may lead to a paradigm shift in disease management

State-of-the-art in product service-systems

A Product Service-System (PSS) is an integrated combination of products and services. This western concept embraces a service-led competitive strategy, environmental sustainability, and the basis to differentiate from competitors who simply offer lower priced products. This paper aims to report the state-of-the-art of PSS research by presenting a clinical review of literature currently available on this topic. The literature is classified and the major outcomes of each study are addressed and analysed. On this basis, this paper defines the PSS concept, reports on its origin and features, gives examples of applications along with potential benefits and barriers to adoption, summarises available tools and methodologies, and identifies future research challenges

Teaching tolerance

Babies born with Pompe disease require life-long treatment with enzyme-replacement therapy (ERT). Despite the human origin of the therapy, recombinant human lysosomal acid α glucosidase (GAA, rhGAA), ERT unfortunately leads to the development of high titers of anti-rhGAA antibody, decreased effectiveness of ERT, and a fatal outcome for a significant number of children who have Pompe disease. The severity of disease, anti-drug antibody (ADA) development, and the consequences thereof are directly related to the degree of the enzyme deficiency. Babies born with a complete deficiency GAA are said to have cross-reactive immunologic material (CRIM)–negative Pompe disease and are highly likely to develop GAA ADA. Less frequently, GAA ADA develop in CRIM-positive individuals. Currently, GAA-ADA sero-positive babies are treated with a combination of immunosuppressive drugs to induce immunological tolerance to ERT, but the long-term effect of these regimens is unknown. Alternative approaches that might redirect the immune response toward antigen-specific tolerance without immunosuppressive agents are needed. Methods leading to the induction of antigen-specific regulatory T cells (Tregs), using peptides such as Tregitopes (T regulatory cell epitopes) are under consideration for the future treatment of CRIM-negative Pompe disease. Tregitopes are natural T cell epitopes derived from immunoglobulin G (IgG) that cause the expansion and activation of regulatory T cells (Treg). Teaching the immune system to tolerate GAA by co-delivering GAA with Tregitope peptides might dramatically improve the lives of CRIM-negative babies and could be applied to other enzyme replacement therapies to which ADA have been induced

Investigating the effect of relationship satisfaction on postpartum women's health-related quality of life in Burkina Faso: a cross-sectional analysis

INTRODUCTION: The period following childbirth poses physiological, physical, social and psychological challenges to women that may affect their quality of life. Few studies in Africa have explored women's health-related quality of life (HrQoL) and its determinants in postpartum populations, including the quality of women's relationships with their male partners. We investigated whether relationship satisfaction was associated with better HrQoL among postpartum women in Burkina Faso, 8 months after childbirth. METHODS: We analysed data from 547 women from the control arm of a randomised controlled trial in Burkina Faso. The study outcome was a woman's HrQoL, assessed using the cross-culturally validated WHOQOL-BREF tool, with response categories adapted for Burkina Faso. The exposure was relationship satisfaction measured using questions adapted from the Dyadic Adjustment Scale and Marital Assessment Test tools. We calculated the median HrQOL scores for the study sample, overall and for each domain of HrQOL (physical, psychological, social and environmental). The association between relationship satisfaction and HrQoL was examined using multiple linear regression models with robust SEs. RESULTS: Postpartum women had high median HrQoL scores in the physical (88.1), psychological (93.1), social (86.1) and environmental (74.0) domains and overall HrQoL (84.0). We found that higher relationship satisfaction is associated with increased HrQoL. After adjusting for potential confounders, we found that for each point increase in relationship satisfaction score, the increase in HrQoL was 0.39 (p<0.001) for the overall HrQoL; 0.32 (p=0.013) for the physical domain; 0.25 (p=0.037) for the psychological domain; 0.46 (p<0.001) for the social domain and 0.49 (p<0.001) for the environmental domain. CONCLUSION: Higher relationship satisfaction is associated with higher HrQoL scores. Policies should aim to support women to cope with the challenges of childbirth and childcare in the postpartum period to improve postpartum women's HrQoL