Multimodal, broadly neutralizing antibodies against SARS-CoV-2 identified by high-throughput native pairing of BCRs from bulk B cells.

TruAB Discovery is an approach that integrates cellular immunology, high-throughput immunosequencing, bioinformatics, and computational biology in order to discover naturally occurring human antibodies for prophylactic or therapeutic use. We adapted our previously described pairSEQ technology to pair B cell receptor heavy and light chains of SARS-CoV-2 spike protein-binding antibodies derived from enriched antigen-specific memory B cells and bulk antibody-secreting cells. We identified approximately 60,000 productive, in-frame, paired antibody sequences, from which 2,093 antibodies were selected for functional evaluation based on abundance, isotype and patterns of somatic hypermutation.

Bivalent intra-spike binding provides durability against emergent Omicron lineages: Results from a global consortium.

The SARS-CoV-2 Omicron variant of concern (VoC) and its sublineages contain 31-36 mutations in spike and escape neutralization by most therapeutic antibodies. In a pseudovirus neutralization assay, 66 of the nearly 400 candidate therapeutics in the Coronavirus Immunotherapeutic Consortium (CoVIC) panel neutralize Omicron and multiple Omicron sublineages. Among natural immunoglobulin Gs (IgGs), especially those in the receptor-binding domain (RBD)-2 epitope community, nearly all Omicron neutralizers recognize spike bivalently, with both antigen-binding fragments (Fabs) simultaneously engaging adjacent RBDs on the same spike.

Fundamental immune-oncogenicity trade-offs define driver mutation fitness.

Missense driver mutations in cancer are concentrated in a few hotspots. Various mechanisms have been proposed to explain this skew, including biased mutational processes, phenotypic differences and immunoediting of neoantigens; however, to our knowledge, no existing model weighs the relative contribution of these features to tumour evolution. We propose a unified theoretical 'free fitness' framework that parsimoniously integrates multimodal genomic, epigenetic, transcriptomic and proteomic data into a biophysical model of the rate-limiting processes underlying the fitness advantage conferred on cancer cells by driver gene mutations.

Multiple early factors anticipate post-acute COVID-19 sequelae.

Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data and patient-reported symptoms.

Examining Environmental Predictors of Community Participation for Adults with Autism Spectrum Disorder Using Geographic Information Systems (GIS).

A geographic information system (GIS) approach systematically assessed whether population density and distribution of community resources contributed to caregiver reported community participation outcomes for 124 adults with autism spectrum disorder (ASD). Regression analyses examined whether GIS measures predicted community participation in areas of social activities and use of services, while also accounting for adult age, conversation ability, and daily living skills (DLS). Results indicated that in addition to person factors of greater DLS and better conversation ability, access to specific community features, such as bus stops, contributed to improved participation.

Magnitude and Dynamics of the T-Cell Response to SARS-CoV-2 Infection at Both Individual and Population Levels.

T cells are involved in the early identification and clearance of viral infections and also support the development of antibodies by B cells. This central role for T cells makes them a desirable target for assessing the immune response to SARS-CoV-2 infection. Here, we combined two high-throughput immune profiling methods to create a quantitative picture of the T-cell response to SARS-CoV-2.

A large-scale database of T-cell receptor beta (TCRβ) sequences and binding associations from natural and synthetic exposure to SARS-CoV-2.

We describe the establishment and current content of the ImmuneCODE™ database, which includes hundreds of millions of T-cell Receptor (TCR) sequences from over 1,400 subjects exposed to or infected with the SARS-CoV-2 virus, as well as over 135,000 high-confidence SARS-CoV-2-specific TCRs. This database is made freely available, and the data contained in it can be downloaded and analyzed online or offline to assist with the global efforts to understand the immune response to the SARS-CoV-2 virus and develop new interventions.

Assessing the convergence of self-report and informant measures for adults with autism spectrum disorder.

Self-report measures are frequently used for research and clinical assessments of adults with autism spectrum disorder. However, there has been little research examining agreement between self-report and informant-report in this population. Valid self-report measures are essential for conducting research with and providing high quality clinical services for adults with autism spectrum disorder.

Safety Evaluation of a 405-nm LED Device for Direct Antimicrobial Treatment of the Murine Brain.

Antimicrobial resistance is a growing problem in human medicine that extends to biomedical research. Compared with chemical-based therapies, light-based therapies present an alternative to traditional pharmaceuticals and are less vulnerable to acquired bacterial resistance. Due to immunologic privilege and relative tissue sensitivity to topical antibiotics, the brain poses a unique set of difficulties with regard to antimicrobial therapy.

Understanding Service Usage and Needs for Adults with ASD: The Importance of Living Situation.

With the increasing prevalence of adults with autism spectrum disorder (ASD), research examining the service experiences of this population is greatly needed. The current study investigated service use, unmet needs, and obstacles to service access for a large sample of adults with ASD. After accounting for various demographic factors known to impact service usage and needs, living situation was a significant predictor of service use, needs, and obstacles to services.

Brief Report: Developmental Trajectories of Adaptive Behavior in Children and Adolescents with ASD.

Research suggests that individuals with autism spectrum disorder (ASD) have significant difficulties with adaptive behavior skills including daily living and functional communication skills. Few studies have examined the developmental trajectory of adaptive behavior across childhood and adolescence. The present study examined longitudinal trajectories of adaptive behavior in a community-based clinic sample of 186 individuals with ASD.

Patterns of Age-Related Cognitive Differences in Adults with Autism Spectrum Disorder.

Little is known about age-related cognitive differences in autism spectrum disorder (ASD). However, given the overlap in cognitive impairments in ASD to those seen in typical aging, it is possible that adults with ASD will face even greater cognitive difficulties as they age. The current study used a cross-sectional design to examine age-related cognitive differences in adults with ASD and age and IQ-matched adults with typical development (age range 30-67 years).

Immunosequencing identifies signatures of cytomegalovirus exposure history and HLA-mediated effects on the T cell repertoire.

An individual's T cell repertoire dynamically encodes their pathogen exposure history. To determine whether pathogen exposure signatures can be identified by documenting public T cell receptors (TCRs), we profiled the T cell repertoire of 666 subjects with known cytomegalovirus (CMV) serostatus by immunosequencing. We developed a statistical classification framework that could diagnose CMV status from the resulting catalog of TCRβ sequences with high specificity and sensitivity in both the original cohort and a validation cohort of 120 different subjects.

Immune Toxicities Elicted by CTLA-4 Blockade in Cancer Patients Are Associated with Early Diversification of the T-cell Repertoire.

While immune checkpoint blockade elicits efficacious responses in many patients with cancer, it also produces a diverse and unpredictable number of immune-related adverse events (IRAE). Mechanisms driving IRAEs are generally unknown. Because CTLA-4 blockade leads to proliferation of circulating T cells, we examined in this study whether ipilimumab treatment leads to clonal expansion of tissue-reactive T cells.

Discovery of T Cell Receptor β Motifs Specific to HLA-B27-Positive Ankylosing Spondylitis by Deep Repertoire Sequence Analysis.

Objective: Ankylosing spondylitis (AS), a chronic inflammatory disorder, has a notable association with HLA-B27. One hypothesis suggests that a common antigen that binds to HLA-B27 is important for AS disease pathogenesis. This study was undertaken to determine sequences and motifs that are shared among HLA-B27-positive AS patients, using T cell repertoire next-generation sequencing.

Multiplex Identification of Antigen-Specific T Cell Receptors Using a Combination of Immune Assays and Immune Receptor Sequencing.

Monitoring antigen-specific T cells is critical for the study of immune responses and development of biomarkers and immunotherapeutics. We developed a novel multiplex assay that combines conventional immune monitoring techniques and immune receptor repertoire sequencing to enable identification of T cells specific to large numbers of antigens simultaneously. We multiplexed 30 different antigens and identified 427 antigen-specific clonotypes from 5 individuals with frequencies as low as 1 per million T cells.

Detection of classical Hodgkin lymphoma specific sequence in peripheral blood using a next-generation sequencing approach.

We applied a highly sensitive next-generation sequencing method to identify lymphoma-specific immunoglobulin gene segments in classical Hodgkin lymphoma (CHL) at initial diagnosis or recurrence, and assessed the ability of detecting such lymphoma-specific sequences in peripheral blood (PB). Seventeen CHL cases were tested and lymphoma-specific sequences were identified in 12 of the primary tumour biopsies. In 11 of these patients whose paired PB samples were available, tumour-specific clonotypes were detected in PB in eight patients.

Decision-making skills in ASD: performance on the Iowa Gambling Task.

Decision making plays a key role in daily function, but little is known regarding how individuals with autism spectrum disorder (ASD) make decisions. The present studies examined decision making in persons with ASD using the Iowa Gambling Task (IGT), a computerized card game with the goal of earning money by deciding among decks of cards. To be successful, players need to figure out which decks are associated with winning and which are associated with losing money in the long run.

The role of mirroring and mentalizing networks in mediating action intentions in autism.

Background: The ability to interpret agents' intent from their actions is a vital skill in successful social interaction. However, individuals with autism spectrum disorders (ASD) have been found to have difficulty in attributing intentions to others. The present study investigated the neural mechanisms of inferring intentions from actions in individuals with ASD.

Motor learning in individuals with autism spectrum disorder: activation in superior parietal lobule related to learning and repetitive behaviors.

Motor-linked implicit learning is the learning of a sequence of movements without conscious awareness. Although motor symptoms are frequently reported in individuals with autism spectrum disorder (ASD), recent behavioral studies have suggested that motor-linked implicit learning may be intact in ASD. The serial reaction time (SRT) task is one of the most common measures of motor-linked implicit learning.

Rule-based category learning in Down syndrome.

Rule-based category learning was examined in youths with Down syndrome (DS), youths with intellectual disability (ID), and typically developing (TD) youths. Two tasks measured category learning: the Modified Card Sort task (MCST) and the Concept Formation test of the Woodcock-Johnson-III ( Woodock, McGrew, & Mather, 2001 ). In regression-based analyses, DS and ID groups performed below the level expected for their nonverbal ability.

Improved survival with T cell clonotype stability after anti-CTLA-4 treatment in cancer patients.

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) blockade can promote antitumor T cell immunity and clinical responses. The mechanism by which anti-CTLA-4 antibodies induces antitumor responses is controversial. To determine the effects of CTLA-4 blockade on the T cell repertoire, we used next-generation deep sequencing to measure the frequency of individual rearranged T cell receptor β (TCRβ) genes, thereby characterizing the diversity of rearrangements, known as T cell clonotypes.