Mutability and hypermutation antagonize immunoglobulin codon optimality.

The efficacy of antibody responses is inherently linked to paratope diversity, as generated through V(D)J recombination and somatic hypermutation. Despite this, it is unclear how genetic diversification mechanisms evolved alongside codon optimality and affect antibody expression. Here, we analyze germline immunoglobulin (IG) genes, natural V(D)J repertoires, serum IgG, and monoclonal antibody (mAb) expression through the lens of codon optimality.

CD4 T cell epitope abundance in ferritin core potentiates responses to hemagglutinin nanoparticle vaccines.

Nanoparticle vaccines based on H. pylori ferritin are increasingly used as a vaccine platform for many pathogens, including RSV, influenza, and SARS-CoV-2. They have been found to elicit enhanced, long-lived B cell responses.

Development of a Mouse Model to Explore CD4 T Cell Specificity, Phenotype, and Recruitment to the Lung after Influenza B Infection.

The adaptive T cell response to influenza B virus is understudied, relative to influenza A virus, for which there has been considerable attention and progress for many decades. Here, we have developed and utilized the C57BL/6 mouse model of intranasal infection with influenza B (B/Brisbane/60/2008) virus and, using an iterative peptide discovery strategy, have identified a series of robustly elicited individual CD4 T cell peptide specificities. The CD4 T cell repertoire encompassed at least eleven major epitopes distributed across hemagglutinin, nucleoprotein, neuraminidase, and non-structural protein 1 and are readily detected in the draining lymph node, spleen, and lung.

Potentiating Lung Mucosal Immunity Through Intranasal Vaccination.

Yearly administration of influenza vaccines is our best available tool for controlling influenza virus spread. However, both practical and immunological factors sometimes result in sub-optimal vaccine efficacy. The call for improved, or even universal, influenza vaccines within the field has led to development of pre-clinical and clinical vaccine candidates that aim to address limitations of current influenza vaccine approaches.

Intranasal Nanoparticle Vaccination Elicits a Persistent, Polyfunctional CD4 T Cell Response in the Murine Lung Specific for a Highly Conserved Influenza Virus Antigen That Is Sufficient To Mediate Protection from Influenza Virus Challenge.

Lung-localized CD4 T cells play a critical role in the control of influenza virus infection and can provide broadly protective immunity. However, current influenza vaccination strategies primarily target influenza hemagglutinin (HA) and are administered peripherally to induce neutralizing antibodies. We have used an intranasal vaccination strategy targeting the highly conserved influenza nucleoprotein (NP) to elicit broadly protective lung-localized CD4 T cell responses.

A Brief Intervention to Support Implementation of Telerehabilitation by Community Rehabilitation Services During COVID-19: A Feasibility Study.

The coronavirus disease 2019 (COVID-19) pandemic has necessitated adoption of telerehabilitation in services where face-to-face consultations were previously standard. We aimed to understand barriers to implementing a telerehabilitation clinical service and design a behavior support strategy for clinicians to implement telerehabilitation. A hybrid implementation study design included pre- and post-intervention questionnaires, identification of key barriers to implementation using the theoretical domains framework, and development of a targeted intervention.

Effect of age on the failure properties of human meniscus: High-speed strain mapping of tissue tears.

The knee meniscus is a soft fibrous tissue with a high incidence of injury in older populations. The objective of this study was to determine the effect of age on the failure behavior of human knee meniscus when applying uniaxial tensile loads parallel or perpendicular to the primary circumferential fiber orientation. Two age groups were tested: under 40 and over 65 years old.

Print-A-Punch: A 3D printed device to cut dumbbell-shaped specimens from soft tissue for tensile testing.

The failure behavior and mechanical properties of soft tissue can be characterized by conducting uniaxial tensile tests on small sectioned specimens, called test coupons. An ideal coupon geometry for tensile testing is a dumbbell shape (dog-bone), yet the cost and time required to fabricate custom steel punches to cut dumbbell-shaped coupons has hindered their universal application in biomechanics research. In this study, we developed an economical and reliable cutting device that can extract dumbbell-shaped coupons from soft biological tissue.

Imprinting and Editing of the Human CD4 T Cell Response to Influenza Virus.

Immunity to influenza is unique among pathogens, in that immune memory is established both via intermittent lung localized infections with highly variable influenza virus strains and by intramuscular vaccinations with inactivated protein-based vaccines. Studies in the past decades have suggested that the B cell responses to influenza infection and vaccination are highly biased by an individual's early history of influenza infection. This reactivity likely reflects both the competitive advantage that memory B cells have in an immune response and the relatively limited diversity of epitopes in influenza hemagglutinin that are recognized by B cells.

Mucosal Mesenchymal Cells: Secondary Barrier and Peripheral Educator for the Gut Immune System.

Stromal connective tissue contains mesenchymal cells, including fibroblasts and myofibroblasts, which line the tissue structure. However, it has been identified that the function of mesenchymal cells is not just structural-they also play critical roles in the creation and regulation of intestinal homeostasis. Thus, mucosal mesenchymal cells instruct intestinal immune cell education (or peripheral immune education) and epithelial cell differentiation thereby shaping the local environment of the mucosal immune system.

Outbreak of Escherichia coli O157:H7 in a child care center in Cook County, Illinois, with prolonged shedding and household transmission.

During the investigation of an outbreak of Escherichia coli O157:H7 in a child care center, illness logs were reviewed and parents interviewed to identify classroom and household exposures. Costs incurred by the center and the public health laboratory were estimated from self-administered questionnaires. We conclude that household transmission played a role in this outbreak and estimate the cost of investigation and intervention at over $6,000 per case.