Engineering of pH-dependent antigen binding properties for toxin-targeting IgG1 antibodies using light-chain shuffling.

Immunoglobulin G (IgG) antibodies that bind their cognate antigen in a pH-dependent manner (acid-switched antibodies) can release their bound antigen for degradation in the acidic environment of endosomes, while the IgGs are rescued by the neonatal Fc receptor (FcRn). Thus, such IgGs can neutralize multiple antigens over time and therefore be used at lower doses than their non-pH-responsive counterparts. Here, we show that light-chain shuffling combined with phage display technology can be used to discover IgG1 antibodies with increased pH-dependent antigen binding properties, using the snake venom toxins, myotoxin II and α-cobratoxin, as examples.

Antibody-dependent enhancement of toxicity of myotoxin II from Bothrops asper.

Improved therapies are needed against snakebite envenoming, which kills and permanently disables thousands of people each year. Recently developed neutralizing monoclonal antibodies against several snake toxins have shown promise in preclinical rodent models. Here, we use phage display technology to discover a human monoclonal antibody and show that this antibody causes antibody-dependent enhancement of toxicity (ADET) of myotoxin II from the venomous pit viper, Bothrops asper, in a mouse model of envenoming that mimics a snakebite.

Phage display assisted discovery of a pH-dependent anti-α-cobratoxin antibody from a natural variable domain library.

Recycling IgG antibodies bind to their target antigen at physiological pH in the blood stream and release them upon endocytosis when pH levels drop, allowing the IgG antibodies to be recycled into circulation via FcRn-mediated cellular pathways, while the antigens undergo lysosomal degradation. This enables recycling antibodies to achieve comparable therapeutic effect at lower doses than their non-recycling counterparts. The development of such antibodies is typically achieved by histidine doping of their variable regions or by performing in vitro antibody selection campaigns utilizing histidine doped libraries.

Deep Mining of Complex Antibody Phage Pools.

An important, and rapidly growing class of drugs are antibodies which can be discovered through phage display technology. In this technique, antibodies are typically first enriched through consecutive rounds of selection on a target antigen with amplification in bacteria between each selection round. Thereafter, a subset of random individual clones is analyzed for binding in a screening procedure.

Advances in antibody phage display technology.

Phage display technology can be used for the discovery of antibodies for research, diagnostic, and therapeutic purposes. In this review, we present and discuss key parameters that can be optimized when performing phage display selection campaigns, including the use of different antibody formats and advanced strategies for antigen presentation, such as immobilization, liposomes, nanodiscs, virus-like particles, and whole cells. Furthermore, we provide insights into selection strategies that can be used for the discovery of antibodies with complex binding requirements, such as targeting a specific epitope, cross-reactivity, or pH-dependent binding.

Protecting the Aging Genome.

Mounting evidence suggests that DNA damage plays a central role in aging. Multiple tiers of defense have evolved to reduce the accumulation of DNA damage, including reducing damaging molecules, repairing DNA damage, and inducing senescence or apoptosis in response to persistent DNA damage. Mutations in or failure of these pathways can lead to accelerated or premature aging and age-related decline in vital organs, supporting the hypothesis that maintaining a pristine genome is paramount for human health.

Bilateral Tubercular Dactylitis: Unusual presentation of an usual disease.

Introduction: Bilateral Tubercular Dactylitis (TD) is an unusual presentation of tuberculosis and only handful numbers of cases are reported in the literature. Hence, very little is known about its clinical presentation, statistic, radiological features and its outcome.

Methods: We have included seven male and two female patients of mean age 7.

Enterotype Variations of the Healthy Human Gut Microbiome in Different Geographical Regions.

Enterotypes are used for classifying individuals based on the gut microbiome. A number of studies are available to find the Enterotypes in healthy individuals; however, most of them lack comparisons at the world level. We analyzed the healthy human gut microbiomes of 495 datasets available in the European Nucleotide Archive (ENA) database derived from fifteen countries from four continents.

Solitary Intramedullary Cervical Cysticercosis without Neurological Deficit: A Rare Case Report.

Neurocysticercosis is commonly seen intracranially and its incidence in the spinal cord is very low. Among spine dorsal region is more common due to more blood flow in this region and it is usually associated with lesion at other sites. The intramedullary location is rarer than extramedullary.

Risk factor distribution for cardiovascular diseases among high school boys and girls of urban Dibrugarh, Assam.

Introduction: Chronic noncommunicable diseases (NCDs) including cardiovascular diseases (CVDs) are the leading cause of death in the world, and their incidence is rising rapidly due to increasing rates of risk factors such as hypertension, dyslipidemia, diabetes, obesity, physical inactivity, and tobacco use. These risk factors track from childhood to adulthood, and their distribution varies among males and females; hence, there is a need to determine risk factor prevalence among adolescent age group so as to plan preventive strategies.

Objective: To determine the distribution of risk factors of CVDs amongst high school boys and girls of urban Dibrugarh, Assam.