e-ISSN: Pending

Browse the failure-mode index

87 real negative results, null findings, and replication failures in Immunology and Microbiology. Search the index →

WASTE indexes published research — it does not host or republish full papers. Each entry is a metadata record compiled from open scholarly databases; the abstract is shown in full only where the paper is openly licensed, otherwise a short excerpt under fair use. Classifications are automated and approximate.

Negative / Null Result ReportOpen accessImmunology and Microbiology

Overcoming resistance to STING agonist therapy to incite durable protective antitumor immunity

Henrique Lemos, Rong Ou, Caroline McCardle et al. · 2020 · Journal for ImmunoTherapy of Cancer

BACKGROUND: Activating the Stimulator of Interferon Genes (STING) adaptor incites antitumor immunity against immunogenic tumors in mice, prompting clinical trials to test STING activators. However, STING signaling in the tumor microenvironment (TME) during development of Lewis lung carcinoma (LLC) suppresses antitumor immunity to promote tumor growth. We hypothesized that local immune balance favoring suppression of antitumor immunity also attenuates antitumor responses following STING activation. The purpose of this study was to evaluate how STING activation impacts antitumor responses in mic

View details →
Negative / Null Result ReportOpen accessImmunology and Microbiology

Recruitment of TLR adapter TRIF to TLR4 signaling complex is mediated by the second helical region of TRIF TIR domain

Wenji Piao, Lisa W. Ru, Kurt H. Piepenbrink et al. · 2013 · Proceedings of the National Academy of Sciences

Toll/IL-1R resistance (TIR) domain-containing adapter-inducing IFN-β (TRIF) is a Toll-like receptor (TLR) adapter that mediates MyD88-independent induction of type I interferons through activation of IFN regulatory factor 3 and NFκB. We…

View details →
Negative / Null Result ReportOpen accessImmunology and Microbiology

Therapeutic Effects of Treatment with Anti-TLR2 and Anti-TLR4 Monoclonal Antibodies in Polymicrobial Sepsis

Cristiano Xavier Lima, Danielle G. Souza, Flávio A. Amaral et al. · 2015 · PLoS ONE

INTRODUCTION: Toll-like receptors (TLRs) play an important role in the recognition of microbial products and in host defense against infection. However, the massive release of inflammatory mediators into the bloodstream following TLR activation following sepsis is thought to contribute to disease pathogenesis. METHODS: Here, we evaluated the effects of preventive or therapeutic administration of monoclonal antibodies (mAbs) targeting either TLR2 or TLR4 in a model of severe polymicrobial sepsis induced by cecal ligation and puncture in mice. RESULTS: Pre-treatment with anti-TLR2 or anti-TLR4 m

View details →
Negative / Null Result ReportImmunology and Microbiology

Functionally Significant Differences in Expression of Disease-Associated IL-7 Receptor α Haplotypes in CD4 T Cells and Dendritic Cells

Edwin Hoe, Fiona C. McKay, Stephen D. Schibeci et al. · 2010 · The Journal of Immunology

Common genetic variants of IL-7 receptor alpha (IL-7Ralpha) have recently been shown to affect susceptibility to multiple sclerosis (MS) and type 1 diabetes, and survival following bone marrow transplantation. Transcription of the gene…

View details →
Negative / Null Result ReportOpen accessImmunology and Microbiology

Kinetics of peripheral blood neutrophils in severe coronavirus disease 2019

Mieke Metzemaekers, Seppe Cambier, Marfa Blanter et al. · 2021 · Clinical & Translational Immunology

OBJECTIVES: Emerging evidence of dysregulation of the myeloid cell compartment urges investigations on neutrophil characteristics in coronavirus disease 2019 (COVID-19). We isolated neutrophils from the blood of COVID-19 patients receiving…

View details →
Negative / Null Result ReportOpen accessImmunology and Microbiology

Pathogenic virus-specific T cells cause disease during treatment with the calcineurin inhibitor FK506: implications for transplantation

Koichi Araki, Shivaprakash Gangappa, Dirck L. Dillehay et al. · 2010 · The Journal of Experimental Medicine

Recently, several cases of fatal lymphocytic choriomeningitis virus (LCMV) infection occurred in transplant recipients being treated with the immunosuppressive calcineurin inhibitor FK506. These findings were surprising because LCMV is a…

View details →
Negative / Null Result ReportOpen accessImmunology and Microbiology

Adjuvant dendritic cell therapy in stage IIIB/C melanoma: the MIND-DC randomized phase III trial

Kalijn F. Bol, Gerty Schreibelt, Martine Bloemendal et al. · 2024 · Nature Communications

Autologous natural dendritic cells (nDCs) treatment can induce tumor-specific immune responses and clinical responses in cancer patients. In this phase III clinical trial (NCT02993315), 148 patients with resected stage IIIB/C melanoma were randomized to adjuvant treatment with nDCs (n = 99) or placebo (n = 49). Active treatment consisted of intranodally injected autologous CD1c+ conventional and plasmacytoid DCs loaded with tumor antigens. The primary endpoint was the 2-year recurrence-free survival (RFS) rate, whereas the secondary endpoints included median RFS, 2-year and median overall surv

View details →
Negative / Null Result ReportOpen accessImmunology and Microbiology

The determinant of periodicity in Mycoplasma pneumoniae incidence: an insight from mathematical modelling

Ryosuke Omori, Yukihiko Nakata, Heidi L. Tessmer et al. · 2015 · Scientific Reports

Until the early 1990 s, incidences of Mycoplasma pneumoniae (MP) infection showed three to five year epidemic cycles in multiple countries, however, the mechanism for the MP epidemic cycle has not been understood. Here, we investigate the determinant of periodicity in MP incidence by employing a mathematical model describing MP transmission dynamics. Three candidates for the determinant of periodicity were evaluated: school-term forcing, minor variance in the duration of immunity, and epidemiological interference between MP serotypes. We find that minor variation in the duration of immunity at

View details →
Negative / Null Result ReportOpen accessImmunology and Microbiology

TCR repertoire diversity in Multiple Sclerosis: High-dimensional bioinformatics analysis of sequences from brain, cerebrospinal fluid and peripheral blood

Roberta Amoriello, Maria Chernigovskaya, Victor Greiff et al. · 2021 · EBioMedicine

BACKGROUND: T cells play a key role in the pathogenesis of multiple sclerosis (MS), a chronic, inflammatory, demyelinating disease of the central nervous system (CNS). Although several studies recently investigated the T-cell receptor…

View details →
Negative / Null Result ReportImmunology and Microbiology

Comparing identified and statistically significant lipids and polar metabolites in 15‐year old serum and dried blood spot samples for longitudinal studies

Jennifer Kyle, Cameron Casey, Kelly G. Stratton et al. · 2016 · Rapid Communications in Mass Spectrometry

RATIONALE: The use of dried blood spots (DBS) has many advantages over traditional plasma and serum samples such as the smaller blood volume required, storage at room temperature, and ability to sample in remote locations. However,…

View details →
Negative / Null Result ReportOpen accessImmunology and Microbiology

Penaeus monodon is protected against gill- associated virus by muscle injection but not oral delivery of bacterially expressed dsRNAs

Melony J. Sellars, M Rao, SJ Arnold et al. · 2011 · Diseases of Aquatic Organisms

Gill-associated virus (GAV) is a nidovirus that commonly infects Penaeus monodon (black tiger shrimp) in eastern Australia, causing morbidity and mortalities in the acute stage of disease. Here we explored the possibility of inhibiting GAV…

View details →
Negative / Null Result ReportOpen accessImmunology and Microbiology

Secretion of Mast Cell Inflammatory Mediators Is Enhanced by CADM1-Dependent Adhesion to Sensory Neurons

Rania Magadmi, Judit Mészáros, Zoheir A. Damanhouri et al. · 2019 · Frontiers in Cellular Neuroscience

Neuroimmune interactions are important in the pathophysiology of many chronic inflammatory diseases, particularly those associated with alterations in sensory processing and pain. Mast cells and sensory neuron nerve endings are found in areas of the body exposed to the external environment; both are specialized to sense potential damage by injury or pathogens and signal to the immune system and nervous system respectively, to elicit protective responses. Cell adhesion molecule 1 (CADM1), also known as SynCAM1, has previously been identified as an adhesion molecule which may couple mast cells t

View details →
Negative / Null Result ReportOpen accessImmunology and Microbiology

Interferons and interferon-related pathways in heart disease

Duc Tin Tran, Sri Nagarjun Batchu, Andrew Advani · 2024 · Frontiers in Cardiovascular Medicine

Interferons (IFNs) and IFN-related pathways play key roles in the defence against microbial infection. However, these processes may also be activated during the pathogenesis of non-infectious diseases, where they may contribute to organ injury, or function in a compensatory manner. In this review, we explore the roles of IFNs and IFN-related pathways in heart disease. We consider the cardiac effects of type I IFNs and IFN-stimulated genes (ISGs); the emerging role of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway; the seemingly paradoxical effects of the type

View details →
Negative / Null Result ReportOpen accessImmunology and Microbiology

The role of endothelial MERTK during the inflammatory response in lungs

Yitong Li, Erika S. Wittchen, Elizabeth Monaghan-Benson et al. · 2019 · PLoS ONE

As a key homeostasis regulator in mammals, the MERTK receptor tyrosine kinase is crucial for efferocytosis, a process that requires remodeling of the cell membrane and adjacent actin cytoskeleton. Membrane and cytoskeletal reorganization also occur in endothelial cells during inflammation, particularly during neutrophil transendothelial migration (TEM) and during changes in permeability. However, MERTK's function in endothelial cells remains unclear. This study evaluated the contribution of endothelial MERTK to neutrophil TEM and endothelial barrier function. In vitro experiments using primary

View details →
Negative / Null Result ReportOpen accessImmunology and Microbiology

Cytokine-dependent and cytokine-independent roles for Mcl-1: genetic evidence for multiple mechanisms by which Mcl-1 promotes survival in primary T lymphocytes

Alexis Dunkle, Ivan Dzhagalov, Y-W He · 2011 · Cell Death and Disease

Myeloid cell leukemia sequence-1 (Mcl-1) is a critical anti-apoptotic factor in T lymphocytes. However, in spite of the many pro-apoptotic proteins with proposed binding to Mcl-1, the specific interactions by which Mcl-1 regulates primary T-cell survival under different conditions have not been fully explored. Further, how different trophic cytokines modulate the specific role(s) of Mcl-1 is unknown. Here, we use genetic mouse models to dissect the roles of Mcl-1 in primary T lymphocytes. Using the inducible Mcl-1-floxed estrogen receptor-Cre fusion protein (Mcl-1(f/f)ERCre) deletion system in

View details →
Negative / Null Result ReportOpen accessImmunology and Microbiology

Evaluation of host genetic and viral factors as surrogate markers for HTLV‐1‐associated myelopathy/tropical spastic paraparesis in Peruvian HTLV‐1‐infected patients

Michael Talledo, Giovanni López, Jeroen R. Huyghe et al. · 2010 · Journal of Medical Virology

Human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a complication that affects up to 5% of HTLV-1-infected individuals. Several host genetic and viral factors have been associated with the…

View details →
Negative / Null Result ReportOpen accessImmunology and Microbiology

Education on tick bite and Lyme borreliosis prevention, aimed at schoolchildren in the Netherlands: comparing the effects of an online educational video game versus a leaflet or no intervention

D. Beaujean, Fedor Gassner, A Wong et al. · 2016 · BMC Public Health

BACKGROUND: Lyme disease or Lyme borreliosis (LB) is the most common tick-borne disease both in the United States and Europe. Children, in particular, are at high risk of contracting LB. Since child-specific educational tools on ticks, tick bites and LB are lacking, we developed an online educational video game. In this study, we compared the effectiveness of an online educational video game versus a newly developed leaflet aimed to improve prevention of tick bites and LB among Dutch schoolchildren. METHODS: A total of 887 children, aged 9-13 years and attending the two final years of primary

View details →
Failed Experiment ReportOpen accessImmunology and Microbiology

Adjuvant MUC vaccination with tecemotide after resection of colorectal liver metastases: a randomized, double-blind, placebo-controlled, multicenter AIO phase II trial (LICC)

Carl Christoph Schimanski, Stefan Kasper, Susanna Hegewisch‐Becker et al. · 2020 · OncoImmunology

= .2141), respectively. Cox regression models revealed no dependence of RFS or OS on MUC1 expression. The most common tecemotide-related grade 3/4 adverse events were diarrhea, injection site reaction, intestinal perforation, peritonitis…

View details →
Negative / Null Result ReportOpen accessImmunology and Microbiology

Combination of IL-2, rapamycin, DNA methyltransferase and histone deacetylase inhibitors for the expansion of human regulatory T cells

Makoto Miyara, Driss Chader, Aude Burlion et al. · 2016 · Oncotarget

// Makoto Miyara 1,2 , Driss Chader 1,2 , Aude Burlion 2 , Jérémie Goldstein 2 , Delphine Sterlin 1,2 , Françoise Norol 3 , Hélène Trebeden-Nègre 3 , Laetitia Claër 1,2 , Shimon Sakaguchi 4,* , Gilles Marodon 2,* , Zahir Amoura 1,2,5,6,* and Guy Gorochov 1,2,6 1 Department of immunology, AP-HP Pitié Salpêtrière, Paris, France 2 Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France 3 Cell Therapy, AP-HP Pitié Salpêtri&egrave

View details →
Negative / Null Result ReportOpen accessImmunology and Microbiology

The Helminth Parasite Heligmosomoides polygyrus Attenuates EAE in an IL-4Rα-Dependent Manner

Madeleine P. J. White, Chris Johnston, John R. Grainger et al. · 2020 · Frontiers in Immunology

Helminth parasites are effective in biasing Th2 immunity and inducing regulatory pathways that minimise excessive inflammation within their hosts, thus allowing chronic infection to occur whilst also suppressing bystander atopic or autoimmune diseases. Multiple sclerosis (MS) is a severe autoimmune disease characterised by inflammatory lesions within the central nervous system; there are very limited therapeutic options for the progressive forms of the disease and none are curative. Here, we used the experimental autoimmune encephalomyelitis (EAE) model to examine if the intestinal helminth He

View details →
Failed Experiment ReportOpen accessImmunology and Microbiology

Retargeting Oncolytic Vesicular Stomatitis Virus to Human T-Cell Lymphotropic Virus Type 1-Associated Adult T-Cell Leukemia

Dillon M. Betancourt, Juan Carlos Ramos, Glen N. Barber · 2015 · Journal of Virology

UNLABELLED: Adult T cell leukemia/lymphoma (ATL) is an aggressive cancer of CD4/CD25(+) T lymphocytes, the etiological agent of which is human T-cell lymphotropic virus type 1 (HTLV-1). ATL is highly refractory to current therapies, making…

View details →
Negative / Null Result ReportOpen accessImmunology and Microbiology

HIV-1 Nef Is Transferred from Expressing T Cells to Hepatocytic Cells through Conduits and Enhances HCV Replication

In-Woo Park, Yan Fan, Xiaoyu Luo et al. · 2014 · PLoS ONE

HIV-1 infection enhances HCV replication and as a consequence accelerates HCV-mediated hepatocellular carcinoma (HCC). However, the precise molecular mechanism by which this takes place is currently unknown. Our data showed that infectious HIV-1 failed to replicate in human hepatocytic cell lines. No discernible virus replication was observed, even when the cell lines transfected with HIV-1 proviral DNA were co-cultured with Jurkat T cells, indicating that the problem of liver deterioration in the co-infected patient is not due to the replication of HIV-1 in the hepatocytes of the HCV infected

View details →
Negative / Null Result ReportOpen accessImmunology and Microbiology

The Success Rate of New Drug Development in Clinical Trials: Crohn’s Disease

Jayson L. Parker, Jillian Clare Köhler · 2010 · Journal of Pharmacy & Pharmaceutical Sciences

PURPOSE: To determine the risk of drug failure during clinical trial testing in Crohn's disease and determine what steps can be taken to improve outcomes. This is the first study to quantify such risk for a single disease. METHODS: Moderate to severe Crohn's disease was investigated by reviewing press releases from 1998 to June 2008. Clinical trial failure causes were classified as commercial or clinical and compared with industry expectations. The risk of failure was also reviewed based on whether the compound was a small molecule drug or a biologic. Lastly, the role of the sponsor was examin

View details →
Negative / Null Result ReportOpen accessImmunology and Microbiology

Innate immunity gene polymorphisms and the risk of colorectal neoplasia

C. M. Chang, Victoria M. Chia, Marc J. Gunter et al. · 2013 · Carcinogenesis

Inherited variation in genes that regulate innate immunity and inflammation may contribute to colorectal neoplasia risk. To evaluate this association, we conducted a nested case-control study of 451 colorectal cancer cases, 694 colorectal…

View details →
Negative / Null Result ReportOpen accessImmunology and Microbiology

APOBEC3G and APOBEC3F Act in Concert To Extinguish HIV-1 Replication

John F. Krisko, Nurjahan Begum, Caroline E. Baker et al. · 2016 · Journal of Virology

UNLABELLED: The multifunctional HIV-1 accessory protein Vif counters the antiviral activities of APOBEC3G (A3G) and APOBEC3F (A3F), and some Vifs counter stable alleles of APOBEC3H (A3H). Studies in humanized mice have shown that HIV-1…

View details →
Negative / Null Result ReportOpen accessImmunology and Microbiology

Impact of a mobile decision support tool on antimicrobial stewardship indicators in St. John’s, Canada

Daniel Doyle, Gerald McDonald, Claire Pratt et al. · 2021 · PLoS ONE

OBJECTIVES: Inappropriate antibiotic use contributes to antimicrobial resistance. The SpectrumTM app provides antibiotic decision support, based on local antimicrobial resistance rates. We determined the impact of regional implementation of the app on inpatient antimicrobial appropriateness, inpatient antimicrobial usage (AMU), population-based Clostridioides difficile infection (CDI) rates and cost, using a retrospective, before and after quasi-experimental design, including a one-year study period. METHODS: The SpectrumTM app was released to prescribers in February, 2019. We performed two on

View details →
Negative / Null Result ReportOpen accessImmunology and Microbiology

A triad of somatic mutagenesis converges in self-reactive B cells to cause a virus-induced autoimmune disease

Clara Young, Mandeep Singh, Katherine Jackson et al. · 2025 · Immunity

The unexplained association between infection and autoimmune disease is strongest for hepatitis C virus-induced cryoglobulinemic vasculitis (HCV-cryovas). To analyze its origins, we traced the evolution of pathogenic rheumatoid factor (RF) autoantibodies in four HCV-cryovas patients by deep single-cell multi-omic analysis, revealing three sources of B cell somatic mutation converged to drive the accumulation of a large disease-causing clone. A method for quantifying low-affinity binding revealed recurring antibody variable domain combinations created by V(D)J recombination that bound self-immu

View details →
Negative / Null Result ReportOpen accessImmunology and Microbiology

Hemodiafiltration Decreases Serum Levels of Inflammatory Mediators in Severe Leptospirosis: A Prospective Study

Sergio Cleto, Camila Eleutério Rodrigues, Ceila María Sant’Ana Malaque et al. · 2016 · PLoS ONE

BACKGROUND: Leptospirosis is a health problem worldwide. Its most severe form is a classic model of sepsis, provoking acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI), with associated mortality that remains unacceptably high. We previously demonstrated that early initiation of sustained low-efficiency dialysis (SLED) followed by daily SLED significantly decreases mortality. However, the mode of clearance can also affect dialysis patient outcomes. Therefore, the objective of this study was to compare the effects of SLED with traditional (diffusive) clearance, via hemodia

View details →
Negative / Null Result ReportOpen accessImmunology and Microbiology

Shaping Neonatal Immunization by Tuning the Delivery of Synergistic Adjuvants via Nanocarriers

Soumik Barman, Francesco Borriello, Byron Brook et al. · 2022 · ACS Chemical Biology

) cells, and germinal center (GC) B cells along with the IgG2c-skewed humoral response in vivo. Dual-loaded cGAMP/CL075-PSs did not outperform admixed cGAMP-PS and CL075-PS in vivo. These data validate an optimally designed adjuvantation…

View details →