System vaccinology analysis of predictors and mechanisms of antibody response durability to multiple vaccines in humans.

We performed a systems vaccinology analysis to investigate immune responses in humans to an H5N1 influenza vaccine, with and without the AS03 adjuvant, to identify factors influencing antibody response magnitude and durability. Our findings revealed a platelet and adhesion-related blood transcriptional signature on day 7 that predicted the longevity of the antibody response, suggesting a potential role for platelets in modulating antibody response durability. As platelets originate from megakaryocytes, we explored the effect of thrombopoietin (TPO)-mediated megakaryocyte activation on antibody response longevity.

The single-cell epigenomic and transcriptional landscape of immunity to influenza vaccination.

Emerging evidence indicates a fundamental role for the epigenome in immunity. Here, we mapped the epigenomic and transcriptional landscape of immunity to influenza vaccination in humans at the single-cell level. Vaccination against seasonal influenza induced persistently diminished H3K27ac in monocytes and myeloid dendritic cells (mDCs), which was associated with impaired cytokine responses to Toll-like receptor stimulation.

A system-view of Bordetella pertussis booster vaccine responses in adults primed with whole-cell versus acellular vaccine in infancy.

The increased incidence of whooping cough worldwide suggests that current vaccination against Bordetella pertussis infection has limitations in quality and duration of protection. The resurgence of infection has been linked to the introduction of acellular vaccines (aP), which have an improved safety profile compared with the previously used whole-cell (wP) vaccines. To determine immunological differences between aP and wP priming in infancy, we performed a systems approach of the immune response to booster vaccination.

Modeling human adaptive immune responses with tonsil organoids.

Most of what we know about adaptive immunity has come from inbred mouse studies, using methods that are often difficult or impossible to confirm in humans. In addition, vaccine responses in mice are often poorly predictive of responses to those same vaccines in humans. Here we use human tonsils, readily available lymphoid organs, to develop a functional organotypic system that recapitulates key germinal center features in vitro, including the production of antigen-specific antibodies, somatic hypermutation and affinity maturation, plasmablast differentiation and class-switch recombination.

Adjuvanted H5N1 influenza vaccine enhances both cross-reactive memory B cell and strain-specific naive B cell responses in humans.

There is a need for improved influenza vaccines. In this study we compared the antibody responses in humans after vaccination with an AS03-adjuvanted versus nonadjuvanted H5N1 avian influenza virus inactivated vaccine. Healthy young adults received two doses of either formulation 3 wk apart.

Squalene emulsion-based vaccine adjuvants stimulate CD8 T cell, but not antibody responses, through a RIPK3-dependent pathway.

The squalene-based oil-in-water emulsion (SE) vaccine adjuvant MF59 has been administered to more than 100 million people in more than 30 countries, in both seasonal and pandemic influenza vaccines. Despite its wide use and efficacy, its mechanisms of action remain unclear. In this study we demonstrate that immunization of mice with MF59 or its mimetic AddaVax (AV) plus soluble antigen results in robust antigen-specific antibody and CD8 T cell responses in lymph nodes and non-lymphoid tissues.

Systems Biological Analysis of Immune Response to Influenza Vaccination.

The last decade has witnessed tremendous progress in immunology and vaccinology, owing to several scientific and technological breakthroughs. Systems vaccinology is a field that has emerged at the forefront of vaccine research and development and provides a unique way to probe immune responses to vaccination in humans. The goals of systems vaccinology are to use systems-based approaches to define signatures that can be used to predict vaccine immunogenicity and efficacy and to delineate the molecular mechanisms driving protective immunity.

Antibiotics-Driven Gut Microbiome Perturbation Alters Immunity to Vaccines in Humans.

Emerging evidence indicates a central role for the microbiome in immunity. However, causal evidence in humans is sparse. Here, we administered broad-spectrum antibiotics to healthy adults prior and subsequent to seasonal influenza vaccination.

Spec-seq unveils transcriptional subpopulations of antibody-secreting cells following influenza vaccination.

Vaccines are among the most effective public health tools for combating certain infectious diseases such as influenza. The role of the humoral immune system in vaccine-induced protection is widely appreciated; however, our understanding of how antibody specificities relate to B cell function remains limited due to the complexity of polyclonal antibody responses. To address this, we developed the Spec-seq framework, which allows for simultaneous monoclonal antibody (mAb) characterization and transcriptional profiling from the same single cell.

Th1/Th17 polarization persists following whole-cell pertussis vaccination despite repeated acellular boosters.

In the mid-1990s, whole-cell pertussis (wP) vaccines were associated with local and systemic adverse events that prompted their replacement with acellular pertussis (aP) vaccines in many high-income countries. In the past decade, rates of pertussis disease have increased in children receiving only aP vaccines. We compared the immune responses to aP boosters in individuals who received their initial doses with either wP or aP vaccines using activation-induced marker (AIM) assays.

Refined protocol for generating monoclonal antibodies from single human and murine B cells.

Generating monoclonal antibodies from single B cells is a valuable tool for characterizing the specificity and functional properties of humoral responses. We and others developed protocols that have facilitated major advances in our understanding of B cell development, tolerance, and effector responses to HIV and influenza. Here, we demonstrate various refinements and dramatically reduce the time required to produce recombinant antibodies.

Vision-Based Pose Estimation for Robot-Mediated Hand Telerehabilitation.

Vision-based Pose Estimation (VPE) represents a non-invasive solution to allow a smooth and natural interaction between a human user and a robotic system, without requiring complex calibration procedures. Moreover, VPE interfaces are gaining momentum as they are highly intuitive, such that they can be used from untrained personnel (e.g.

Systems biology of immunity to MF59-adjuvanted versus nonadjuvanted trivalent seasonal influenza vaccines in early childhood.

The dynamics and molecular mechanisms underlying vaccine immunity in early childhood remain poorly understood. Here we applied systems approaches to investigate the innate and adaptive responses to trivalent inactivated influenza vaccine (TIV) and MF59-adjuvanted TIV (ATIV) in 90 14- to 24-mo-old healthy children. MF59 enhanced the magnitude and kinetics of serum antibody titers following vaccination, and induced a greater frequency of vaccine specific, multicytokine-producing CD4(+) T cells.

Gastrocnemius myoelectric control of a robotic hip exoskeleton.

In this paper we present a novel EMG-based assistive control strategy for lower-limb exoskeletons. An active pelvis orthosis (APO) generates torque profiles for the hip flexion motion assistance, according to the Gastrocnemius Medialis EMG signal. The strategy has been tested on one healthy subject: experimental results show that the user is able to reduce his muscular activation when the assistance is switched on with respect to the free walking condition.

Usability test of a hand exoskeleton for activities of daily living: an example of user-centered design.

Purpose: (1) To assess a robotic device (Handexos) during the design process with regard to usability, end user satisfaction and safety, (2) to determine whether Handexos can improve the activities of daily living (ADLs) of spinal cord injury (SCI) patients and stroke patients with upper-limb dysfunction.

Methods: During a 2-year development stage of the device, a total of 37 participants (aged 22-68), 28 clinicians (experts) and nine patients with SCI or stroke (end users) were included in a user-centered design process featuring usability tests. They performed five grasps wearing the device.

Enhancing brain-machine interface (BMI) control of a hand exoskeleton using electrooculography (EOG).

Background: Brain-machine interfaces (BMIs) allow direct translation of electric, magnetic or metabolic brain signals into control commands of external devices such as robots, prostheses or exoskeletons. However, non-stationarity of brain signals and susceptibility to biological or environmental artifacts impede reliable control and safety of BMIs, particularly in daily life environments. Here we introduce and tested a novel hybrid brain-neural computer interaction (BNCI) system fusing electroencephalography (EEG) and electrooculography (EOG) to enhance reliability and safety of continuous hand exoskeleton-driven grasping motions.

Analysis of relative displacement between the HX wearable robotic exoskeleton and the user's hand.

Background: Advances in technology are allowing for the production of several viable wearable robotic devices to assist with activities of daily living and with rehabilitation. One of the most pressing limitations to user satisfaction is the lack of consistency in motion between the user and the robotic device. The displacement between the robot and the body segment may not correspond because of differences in skin and tissue compliance, mechanical backlash, and/or incorrect fit.

Translating glycolytic metabolism to innate immunity in dendritic cells.

Growing evidence supports a role for glycolysis in immune activation. Everts et al. (2014) now show that TLR-mediated stimulation of dendritic cells rapidly induces glycolysis, which regenerates NADPH and TCA intermediates to support fatty acid production.

Kinematics and design of a portable and wearable exoskeleton for hand rehabilitation.

We present the kinematic design and actuation mechanics of a wearable exoskeleton for hand rehabilitation of post-stroke. Our design method is focused on achieving maximum safety, comfort and reliability in the interaction, and allowing different users to wear the device with no manual regulations. In particular, we propose a kinematic and actuation solution for the index finger flexion/extension, which leaves full movement freedom on the abduction-adduction plane.

NEUROExos: A powered elbow orthosis for post-stroke early neurorehabilitation.

This paper presents the development of a portable version of the robotic elbow exoskeleton NEUROExos, designed for the treatment of stroke survivors in acute/sub-acute phases. The design was improved by a novel Series Elastic Actuation (SEA) system. The system implements two control modalities: a near-zero output impedance torque control and a passive-compliance position control.

MF59 and Pam3CSK4 boost adaptive responses to influenza subunit vaccine through an IFN type I-independent mechanism of action.

The innate immune pathways induced by adjuvants required to increase adaptive responses to influenza subunit vaccines are not well characterized. We profiled different TLR-independent (MF59 and alum) and TLR-dependent (CpG, resiquimod, and Pam3CSK4) adjuvants for the ability to increase the immunogenicity to a trivalent influenza seasonal subunit vaccine and to tetanus toxoid (TT) in mouse. Although all adjuvants boosted the Ab responses to TT, only MF59 and Pam3CSK4 were able to enhance hemagglutinin Ab responses.

Vaccine adjuvants alum and MF59 induce rapid recruitment of neutrophils and monocytes that participate in antigen transport to draining lymph nodes.

Vaccine adjuvants such as alum and the oil-in-water emulsion MF59 are used to enhance immune responses towards pure soluble antigens, but their mechanism of action is still largely unclear. Since most adjuvanted vaccines are administered intramuscularly, we studied immune responses in the mouse muscle and found that both adjuvants were potent inducers of chemokine production and promoted rapid recruitment of CD11b(+) cells. The earliest and most abundantly recruited cell type are neutrophils, followed by monocytes, eosinophils and later dendritic cells (DCs) and macrophages.