Associations between family planning, healthcare access, and female education and vaccination among under-immunized children.

Background: Increasing childhood vaccination, family planning, healthcare access, and women's empowerment are targets of the Sustainable Development Goals (SDG). Barriers to healthcare access impede vaccination; tackling goals holistically could create larger gains than siloed efforts. We studied Nepal, Senegal, and Zambia to test the association between childhood vaccinations and other SDG indicators to identify clustered deprivations.

Factors associated with vaccine coverage improvements in Senegal between 2005 and 2019: a quantitative retrospective analysis.

Objective: Senegal has demonstrated catalytic improvements in national coverage rates for early childhood vaccination, despite lower development assistance for childhood vaccines in Senegal compared with other low-income and lower-middle income countries. Understanding factors associated with historical changes in childhood vaccine coverage in Senegal, as well as heterogeneities across its 14 regions, can highlight effective practices that might be adapted to improve vaccine coverage elsewhere.

Design: Childhood vaccination coverage rates, demographic information and health system characteristics were identified from Senegal's Demographic and Health Surveys (DHS) and Senegal national reports for years 2005-2019.

Critical success factors for high routine immunization performance: A case study of Nepal.

Introduction: The essential components of a vaccine delivery system are well-documented, but robust evidence on how and why the related processes and implementation strategies drive catalytic improvements in vaccination coverage are not well established. To address this gap, we identified critical success factors that may have led to substantial improvements in routine childhood immunization coverage in Nepal from 2000 through 2019.

Methods: We identified Nepal as an exemplar in the delivery of early childhood immunization through analysis of DTP1 and DTP3 coverage data.

Critical success factors for routine immunization performance: A case study of Zambia 2000 to 2018.

Introduction: The essential components of a vaccine delivery system are well-documented, but robust evidence on how and why the related processes and implementation strategies prove effective at driving coverage is not well-established. To address this gap, we identified critical success factors associated with advancing key policies and programs that may have led to the substantial changes in routine childhood immunization coverage in Zambia between 2000 and 2018.

Methods: We identified Zambia as an exemplar in the delivery of childhood vaccines through analysis of DTP1 and DTP3 coverage data.

Students' preferences for returning to colleges and universities during the COVID-19 pandemic: A discrete choice experiment.

Importance: When an emerging infectious disease outbreak occurs, such as COVID-19, institutions of higher education (IHEs) must weigh decisions about how to operate their campuses. These decisions entail whether campuses should remain open, how courses should be delivered (in-person, online, or a mixture of the two), and what safety plans should be enacted for those on campus. These issues have weighed heavily on campus administrators during the on-going COVID-19 pandemic.

Antimicrobial effects of chitosan and garlic against Salmonella spp., Escherichia coli O157:H7, and Listeria monocytogenes in hummus during storage at various temperatures.

The study aimed to evaluate the antimicrobial activity of 0.5 or 1% (w/w) chitosan and 1% (w/w) garlic against Salmonella spp., Escherichia coli O157:H7 and Listeria monocytogenes in hummus dip stored at 4, 10, or 25°C for 28, 21, or 7 days, respectively.

Health spending and vaccination coverage in low-income countries.

Introduction: Routine immunisation is a cost-effective way to save lives and protect people from disease. Some low-income countries (LIC) achieved remarkable success in childhood immunisation. Yet, previous studies comparing the relationship between economic growth and health spending with vaccination coverage have been limited.

A Phase I Study of DLYE5953A, an Anti-LY6E Antibody Covalently Linked to Monomethyl Auristatin E, in Patients with Refractory Solid Tumors.

Purpose: DLYE5953A is an antibody-drug conjugate consisting of an anti-LY6E antibody covalently linked to the cytotoxic agent monomethyl auristatin E. This study characterized the safety, pharmacokinetics, immunogenicity, potential biomarkers, and antitumor activity of DLYE5953A in patients with metastatic solid tumors.

Patients And Methods: This was a phase I, open-label, 3+3 dose-escalation, and dose-expansion study of DLYE5953A administered intravenously every 21 days (Q3W) in patients with locally advanced or metastatic solid malignancies.

Comparative Analysis of Thymic and Blood Treg in Myasthenia Gravis: Thymic Epithelial Cells Contribute to Thymic Immunoregulatory Defects.

The thymus is involved in autoimmune Myasthenia gravis (MG) associated with anti-acetylcholine (AChR) antibodies. In MG, thymic regulatory T cells (Treg) are not efficiently suppressive, and conventional T cells (Tconv) are resistant to suppression. To better understand the specific role of the thymus in MG, we compared the phenotype and function of peripheral and thymic Treg and Tconv from controls and MG patients.

Phase I study of the anti-endothelin B receptor antibody-drug conjugate DEDN6526A in patients with metastatic or unresectable cutaneous, mucosal, or uveal melanoma.

Background Endothelin B receptor (ETR) is involved in melanoma pathogenesis and is overexpressed in metastatic melanoma. The antibody-drug conjugate DEDN6526A targets ETR and is comprised of the humanized anti-ETR monoclonal antibody conjugated to the anti-mitotic agent monomethyl auristatin E (MMAE). Methods This Phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and anti-tumor activity of DEDN6526A (0.

Evaluation and use of an anti-cynomolgus monkey CD79b surrogate antibody-drug conjugate to enable clinical development of polatuzumab vedotin.

Background And Purpose: Polatuzumab vedotin is an antibody-drug conjugate (ADC) being developed for non-Hodgkin's lymphoma. It contains a humanized anti-CD79b IgG1 monoclonal antibody linked to monomethyl auristatin E (MMAE), an anti-mitotic agent. Polatuzumab vedotin binds to human CD79b only.

Preclinical and translational pharmacokinetics of a novel THIOMAB™ antibody-antibiotic conjugate against .

DSTA4637S, a novel THIOMAB™ antibody-antibiotic conjugate (TAC) against (), is currently being investigated as a potential therapy for complicated bloodstream infections. DSTA4637S is composed of a monoclonal THIOMAB IgG1 recognizing linked to a rifamycin-class antibiotic (dmDNA31) via a protease-cleavable linker. The pharmacokinetics (PK) of DSTA4637A (a liquid formulation of DSTA4637S) and its unconjugated antibody MSTA3852A were characterized in rats and monkeys.

Immunogenicity of antibody-drug conjugates: observations across 8 molecules in 11 clinical trials.

To evaluate the clinical immunogenicity of eight antibody-drug conjugates (ADCs), multi-domain biotherapeutics that could theoretically pose a greater immunogenicity risk than monoclonal antibodies (mAbs) because they contain non-natural structural motifs. Immunogenicity strategies and assays for these ADCs included those commonly used for conventional biotherapeutics with additional characterization. A tiered approach was adopted for testing Phase I and II clinical study samples with screening, confirmatory assays and additional domain characterization.

Phase 2 Randomized Trial of the Safety and Efficacy of MHAA4549A, a Broadly Neutralizing Monoclonal Antibody, in a Human Influenza A Virus Challenge Model.

MHAA4549A, a human monoclonal antibody targeting the hemagglutinin stalk region of influenza A virus (IAV), is being developed as a therapeutic for patients hospitalized with severe IAV infection. The safety and efficacy of MHAA4549A were assessed in a randomized, double-blind, placebo-controlled, dose-ranging study in a human IAV challenge model. One hundred healthy volunteers were inoculated with A/Wisconsin/67/2005 (H3N2) IAV and, 24 to 36 h later, administered a single intravenous dose of either placebo, MHAA4549A (400, 1,200, or 3,600 mg), or a standard oral dose of oseltamivir.

Effect of storage temperatures and stresses on the survival of Salmonella spp. in halva.

Unlabelled: The presence of Salmonella spp. in halva has been associated with foodborne illnesses and product recalls from the markets. This study investigated the effect of environmental stresses on the survival of Salmonella spp.

Application of a Plug-and-Play Immunogenicity Assay in Cynomolgus Monkey Serum for ADCs at Early Stages of Drug Development.

Immunogenicity assessment during early stages of nonclinical biotherapeutic development is not always warranted. It is rarely predictive for clinical studies and evidence for the presence of anti-drug antibodies (ADAs) may be inferred from the pharmacokinetic (PK) profile. However, collecting and banking samples during the course of the study are prudent for confirmation and a deeper understanding of the impact on PK and safety.

Vaccination Against Hepatitis B Virus (HBV) in HIV-1-Infected Patients With Isolated Anti-HBV Core Antibody: The ANRS HB EP03 CISOVAC Prospective Study.

Background: Although an isolated anti-hepatitis B virus (HBV) core antibody (anti-HBc) serological profile is frequent in human immunodeficiency virus (HIV)-infected patients, data on HBV vaccination in these patients are scarce.

Methods: A prospective multicenter study was conducted to assess the immunogenicity of HBV vaccination in 54 patients with an isolated anti-HBc profile and undetectable HIV load. They were vaccinated with 1 dose (20 µg) of recombinant HBV vaccine.

Semi-mechanistic Multiple-Analyte Pharmacokinetic Model for an Antibody-Drug-Conjugate in Cynomolgus Monkeys.

Purpose: A semi-mechanistic multiple-analyte population pharmacokinetics (PK) model was developed to describe the complex relationship between the different analytes of monomethyl auristatin E (MMAE) containing antibody-drug conjugates (ADCs) and to provide insight regarding the major pathways of conjugate elimination and unconjugated MMAE release in vivo.

Methods: For an anti-CD79b-MMAE ADC the PK of total antibody (Tab), conjugate (evaluated as antibody conjugated MMAE or acMMAE), and unconjugated MMAE were quantified in cynomolgus monkeys for single (0.3, 1, or 3 mg/kg), and multiple doses (3 or 5 mg/kg, every-three-weeks for 4 doses).

Human thymus medullary epithelial cells promote regulatory T-cell generation by stimulating interleukin-2 production via ICOS ligand.

Natural thymic T regulatory (tTreg) cells maintain tolerance to self-antigen. These cells are generated in the thymus, but how this generation occurs is still controversial. Furthermore, the contribution of thymus epithelial cells to this process is still unclear, especially in humans.

Both Treg cells and Tconv cells are defective in the Myasthenia gravis thymus: roles of IL-17 and TNF-α.

Myasthenia gravis (MG) is an autoimmune disease in which the thymus frequently presents follicular hyperplasia and signs of inflammation and T cells display a defect in suppressive regulation. Defects in a suppressive assay can indicate either the defective function of Treg cells or the resistance of Tconv cells to suppression by Treg cells. The aim of this study was to determine which cells were responsible for this defect and to address the mechanisms involved.

DCDT2980S, an anti-CD22-monomethyl auristatin E antibody-drug conjugate, is a potential treatment for non-Hodgkin lymphoma.

Antibody-drug conjugates (ADC), potent cytotoxic drugs linked to antibodies via chemical linkers, allow specific targeting of drugs to neoplastic cells. We have used this technology to develop the ADC DCDT2980S that targets CD22, an antigen with expression limited to B cells and the vast majority of non-Hodgkin lymphomas (NHL). DCDT2980S consists of a humanized anti-CD22 monoclonal IgG1 antibody with a potent microtubule-disrupting agent, monomethyl auristatin E (MMAE), linked to the reduced cysteines of the antibody via a protease cleavable linker, maleimidocaproyl-valine-citrulline-p-aminobenzoyloxycarbonyl (MC-vc-PAB).

Defects of immunoregulatory mechanisms in myasthenia gravis: role of IL-17.

Deficient immunoregulation is consistently observed in autoimmune diseases. Here, we summarize the abnormalities of the T cell response in autoimmune myasthenia gravis (MG) by focusing on activation markers, inflammatory features, and imbalance between the different T cell subsets, including Th17 and regulatory T cells (T(reg) cells). In the thymus from MG patients, T(reg) cell numbers are normal while their suppressive function is severely defective, and this defect could not be explained by contaminating effector CD127(low) T cells.

Apolipoprotein E-deficient mice develop an anti-Chlamydophila pneumoniae T helper 2 response and resist vascular infection.

Background: Hypercholesterolemia could inhibit the immune response against various pathogens. No information is available about its impact on the immune response toward Chlamydophila pneumoniae.

Methods: Apolipoprotein E (apoE)-deficient and wild-type mice fed a normal diet were infected with a single intranasal inoculation of viable C.

Chlamydia pneumoniae alters mildly oxidized low-density lipoprotein-induced cell death in human endothelial cells, leading to necrosis rather than apoptosis.

Background: Atherosclerosis is characterized by oxidative stress that induces lipid and protein oxidation in the vascular wall. Oxidized low-density lipoproteins (oxLDLs) are present in lesions, and one of their actions is to induce apoptosis or necrosis in vascular cells. A role for Chlamydia pneumoniae in atherosclerosis has been proposed, but the mechanisms involved remain largely unknown.