Immunomonitoring of human responses to the rVSV-ZEBOV Ebola vaccine

The rVSV-ZEBOV vaccine is currently the only Ebola vaccine with demonstrated clinical efficacy in a ring-vaccination clinical trial. It has been shown to be reactogenic but immunogenic and safe in several Phase I clinical studies. However, its mechanisms of protection are unknown and available immunogenicity data are mostly limited to classical serological analysis; it is now of paramount importance to apply cutting-edge technologies, including transcriptomic and metabolomic analyses, and to perform integrative analyses with standard serology and clinical data to comprehensively profile the rVSV-ZEBOV immune signature

Visual Odometry and Trajectory Reconstruction for UAVs

The growing popularity of systems based on Unmanned Aerial Vehicles (UAVs) is highlighting their vulnerability particularly in relation to the positioning system used. Typically, UAV architectures use the civilian GPS which is exposed to a number of different attacks, such as jamming or spoofing. This is why it is important to develop alternative methodologies to accurately estimate the actual UAV position without relying on GPS measurements only. In this paper we propose a position estimate method for UAVs based on monocular visual odometry. We have developed a flight control system capable of keeping track of the entire trajectory travelled, with a reduced dependency on the availability of GPS signal. Moreover, the simplicity of the developed solution makes it applicable to a wide range of commercial drones. The final goal is to allow for safer flights in all conditions, even under cyber-attacks trying to deceive the drone

Profiling the B cell immune response elicited by vaccination against the respiratory virus SARS-CoV-2

B cells play a fundamental role in host defenses against viral infections. Profiling the B cell response elicited by SARS-CoV-2 vaccination, including the generation and persistence of antigen-specific memory B cells, is essential for improving the knowledge of vaccine immune responsiveness, beyond the antibody response. mRNA-based vaccines have shown to induce a robust class-switched memory B cell response that persists overtime and is boosted by further vaccine administration, suggesting that memory B cells are critical in driving a recall response upon re-exposure to SARS-CoV-2 antigens. Here, we focus on the role of the B cell response in the context of SARS-CoV-2 vaccination, offering an overview of the different technologies that can be used to identify spike-specific B cells, characterize their phenotype using machine learning approaches, measure their capacity to reactivate following antigen encounter, and tracking the maturation of the B cell receptor antigenic affinity. Copyright © 2022 Pettini, Medaglini and Ciabattini

Role of the microbiota in the modulation of vaccine immune responses

The human immune system and the microbiota co-evolve, and their balanced relationship is based on crosstalk between the two systems through the course of life. This tight association and the overall composition and richness of the microbiota play an important role in the modulation of host immunity and may impact the immune response to vaccination. The availability of innovative technologies, such as next-generation sequencing (NGS) and correlated bioinformatics tools, allows a deeper investigation of the crosstalk between the microbiota and human immune responses. This review discusses the current knowledge on the influence of the microbiota on the immune response to vaccination and novel tools to deeply analyze the impact of the microbiome on vaccine responses

Using the biomechanical characteristics of the humerus to infer the subsistence economy of the Middle Bronze Age population from Olmo di Nogara (Verona, Italy)

Lo scopo di questa tesi è quello di effettuare un’analisi biomeccanica di un campione di omeri provenienti dalla Necropoli Olmo di Nogara (Verona) risalente al Bronzo Medio (1700-1350 AC). Lo studio delle caratteristiche biomeccaniche dell’osso ci fornisce una serie di variabili la cui analisi statistica, integrata con informazioni archeologiche ed etnografiche, può essere utilizzata per ipotizzare i pattern comportamentali e l’economia di sussistenza delle popolazioni del passato. La biomeccanica è la disciplina che studia le proprietà meccaniche di particolari elementi biologici. L’osso in particolare, in questo caso specifico l’omero, è un elemento che presenta un’alta plasticità, è capace cioè di modificarsi in risposta alle forze che vi vengono applicate apponendo materiale osseo lungo la direzione dove una maggiore resistenza è necessaria. In particolare, in questo studio viene applicato il metodo della Cross-Sectional Geometry (CSG), una tecnica mutuata dell’ingegneria che accomuna un osso lungo (come l’omero) a una trave cava e descrive la distribuzione del materiale (osso nel nostro caso) in ogni sezione trasversale della struttura. Per l’omero viene utilizzata la sezione al livello 35% della lunghezza dell’osso perché a questo livello non ci sono inserzioni muscolari che potrebbero alterare il profilo della sezione. Tutti gli omeri sono stati scannerizzati mediante TAC medica e tramite il programma Avizo si sono ottenute sezioni virtuali per ogni osso. Le sezioni così ottenute sono state elaborate con il programma ImageJ che restituisce le variabili biomeccaniche relative alla resistenza dell’omero alla torsione, curvatura e compressione. La scelta dell’omero come elemento di studio è da ricondursi alla grande quantità di informazioni che si possono estrapolare da quest’osso oltre ai recenti studi che dimostrano quanto la morfologia delle ossa degli arti sia condizionata dall’economia di sussistenza e dal pattern comportamentale della popolazione. In questo caso il campione del Bronzo Medio della necropoli Olmo di Nogara verrà analizzato. Innovazioni dell’Età del Bronzo, infatti, hanno portato a una divisione del lavoro tra uomini e donne nonché a un differente set di movimenti dovuti alla nuova economia di sussistenza. In aggiunta a questo, il ritrovamento di spade nelle tombe di alcuni individui lascia pensare a una qualche sorta di organizzazione militare, sebbene probabilmente non complessa, che potrebbe avere dei riscontri nell’asimmetria della robustezza degli arti superiori, e quindi degli omeri, negli uomini

A stochastic model for CD4+ T cell proliferation and dissemination network in primary immune response

The study of the initial phase of the adaptive immune response after first antigen encounter provides essential information on the magnitude and quality of the immune response. This phase is characterized by proliferation and dissemination of T cells in the lymphoid organs. Modeling and identifying the key features of this phenomenon may provide a useful tool for the analysis and prediction of the effects of immunization. This knowledge can be effectively exploited in vaccinology, where it is of interest to evaluate and compare the responses to different vaccine formulations. The objective of this paper is to construct a stochastic model based on branching process theory, for the dissemination network of antigen-specific CD4+ T cells. The devised model is validated on in vivo animal experimental data. The model presented has been applied to the vaccine immunization context making references to simple proliferation laws that take into account division, death and quiescence, but it can also be applied to any context where it is of interest to study the dynamic evolution of a population. Copyright:© 2015 Boianelli et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Optimized protocol for the detection of multifunctional epitope-specific CD4+ T cells combining MHC-II tetramer and intracellular cytokine staining technologies

Analysis of multifunctional CD4+ T cells is fundamental for characterizing the immune responses to vaccination or infection. Major histocompatibility complex (MHC)/peptide tetramers represent a powerful technology for the detection of antigen-specific T cells by specific binding to their T-cell receptor, and their combination with functional assays is fundamental for characterizing the antigen-specific immune response. Here we optimized a protocol for the detection of multiple intracellular cytokines within epitope-specific CD4+ T cells identified by the MHC class II tetramer technology. The optimal procedure for assessing the functional activity of tetramer-binding CD4+ T cells was based on the simultaneous intracellular staining with both MHC tetramers and cytokine-specific antibodies upon in vitro restimulation of cells with the vaccine antigen. The protocol was selected among procedures that differently combine the steps of cellular restimulation and tetramer staining with intracellular cytokine labeling. This method can be applied to better understand the complex functional profile of CD4+ T-cell responses upon vaccination or infection

innovation partnership for a roadmap on vaccines in europe iprove a vision for the vaccines of tomorrow

Abstract A clear vision for vaccines research and development (R&D) is needed if Europe is to continue to lead the discovery of next generation vaccines. Innovation Partnership for a Roadmap on Vaccines in Europe (IPROVE) is a collaboration between leading vaccine experts to develop a roadmap setting out how Europe can best invest in the science and technology essential for vaccines innovation. This FP7 project, started in December 2013, brought together more than 130 key public and private stakeholders from academia, public health institutes, regulators, industry and small and medium-sized enterprises to determine and prioritise the gaps and challenges to be addressed to bolster innovation in vaccines and vaccination in Europe. The IPROVE consultation process was structured around seven themes: vaccine R&D, manufacturing and quality control, infrastructure, therapeutic vaccines, needs of small and medium-sized enterprises, vaccines acceptance and training needs. More than 80 recommendations were made by the consultation groups, mainly focused on the need for a multidisciplinary research approach to stimulate innovation, accelerated translation of scientific knowledge into technological innovation, and fostering of real collaboration within the European vaccine ecosystem. The consultation also reinforced the fact that vaccines are only as good as their vaccine implementation programmes, and that more must be done to understand and address vaccination hesitancy of both the general public and healthcare professionals. Bringing together a wide range of stakeholders to work on the IPROVE roadmap has increased mutual understanding of their different perspectives, needs and priorities. IPROVE is a first attempt to develop such a comprehensive view of the vaccine sector. This prioritisation effort, aims to help policy-makers and funders identify those vaccine-related areas and technologies where key investment is needed for short and medium-long term success

Distribution of Primed T Cells and Antigen-Loaded Antigen Presenting Cells Following Intranasal Immunization in Mice

Priming of T cells is a key event in vaccination, since it bears a decisive influence on the type and magnitude of the immune response. T-cell priming after mucosal immunization via the nasal route was studied by investigating the distribution of antigen-loaded antigen presenting cells (APCs) and primed antigen-specific T cells. Nasal immunization studies were conducted using the model protein antigen ovalbumin (OVA) plus CpG oligodeoxynucleotide adjuvant. Trafficking of antigen-specific primed T cells was analyzed in vivo after adoptive transfer of OVA-specific transgenic T cells in the presence or absence of fingolimod, a drug that causes lymphocytes sequestration within lymph nodes. Antigen-loaded APCs were observed in mediastinal lymph nodes, draining the respiratory tract, but not in distal lymph nodes. Antigen-specific proliferating T cells were first observed within draining lymph nodes, and later in distal iliac and mesenteric lymph nodes and in the spleen. The presence at distal sites was due to migration of locally primed T cells as shown by fingolimod treatment that caused a drastic reduction of proliferated T cells in non-draining lymph nodes and an accumulation of extensively divided T cells within draining lymph nodes. Homing of nasally primed T cells in distal iliac lymph nodes was CD62L-dependent, while entry into mesenteric lymph nodes depended on both CD62L and α4β7, as shown by in vivo antibody-mediated inhibition of T-cell trafficking. These data, elucidating the trafficking of antigen-specific primed T cells to non-draining peripheral and mucosa-associated lymph nodes following nasal immunization, provide relevant insights for the design of vaccination strategies based on mucosal priming

Shelter from the cytokine storm: pitfalls and prospects in the development of SARS-CoV-2 vaccines for an elderly population

The SARS-CoV-2 pandemic urgently calls for the development of effective preventive tools. COVID-19 hits greatly the elder and more fragile fraction of the population boosting the evergreen issue of the vaccination of older people. The development of a vaccine against SARS-CoV-2 tailored for the elderly population faces the challenge of the poor immune responsiveness of the older population due to immunosenescence, comorbidities, and pharmacological treatments. Moreover, it is likely that the inflammaging phenotype associated with age could both influence vaccination efficacy and exacerbate the risk of COVID-19-related “cytokine storm syndrome” with an overlap between the factors which impact vaccination effectiveness and those that boost virulence and worsen the prognosis of SARS-CoV-2 infection. The complex and still unclear immunopathological mechanisms of SARS-CoV-2 infection, together with the progressive age-related decline of immune responses, and the lack of clear correlates of protection, make the design of vaccination strategies for older people extremely challenging. In the ongoing effort in vaccine development, different SARS-CoV-2 vaccine candidates have been developed, tested in pre-clinical and clinical studies and are undergoing clinical testing, but only a small fraction of these are currently being tested in the older fraction of the population. Recent advances in systems biology integrating clinical, immunologic, and omics data can help to identify stable and robust markers of vaccine response and move towards a better understanding of SARS-CoV-2 vaccine responses in the elderly