scholarly journals High seroreactivity against SARS-CoV-2 Spike epitopes in a pre SARS-CoV-2 cohort: implications for antibody testing and vaccine design

Author(s):  
Kaia Palm ◽  
Mariliis Jaago ◽  
Annika Rahni ◽  
Nadezhda Pupina ◽  
Arno Pihlak ◽  
...  

Little is known about the quality of polyclonal antibody responses in COVID-19 patients, and how it correlates with disease severity or patients' prior exposure to other pathogens. The whole polyclonal antibody repertoire in a retrospective cohort of 538 individuals was mapped against SARS-CoV-2 spike (S) glycoprotein, the main target of antibody immune responses in SARS-CoV-2 infection. Bioinformatic predictions identified 15 major B cell epitopes for S of SARS-CoV-2. Several epitopes localised in RBD of S including those spanning the ACE2-binding site, the highly conserved cryptic epitope of the neutralizing antibody of SARS-CoV, and fusion/entry domains of HR1 and HR2 of S protein of SARS-CoV-2. Intriguingly, some of these epitopes have cross-reactivity to antigens of common pathogens, potentially affecting SARS-CoV-2 infection outcome. High level of anti-Spike SARS-CoV-2 seroreactivity in populations with no history of exposure to SARS-CoV-2 is of clinical relevance and could underpin better understanding of COVID-19 pathophysiology in different populations and provide a blueprint for design of effective vaccines and developing better strategies for antibody testing.

2021 ◽  
Author(s):  
Dionysios Grigoriadis ◽  
Ege Sackey ◽  
Katie Riches ◽  
Malou van Zanten ◽  
Glen Brice ◽  
...  

Lipoedema is a chronic adipose tissue disorder mainly affecting women, causing excess subcutaneous fat deposition on the lower limbs with pain and tenderness. There is often a family history of lipoedema, suggesting a genetic origin, but the contribution of genetics is currently unclear. A tightly phenotyped cohort of 200 lipoedema patients was recruited from two UK specialist clinics. Objective clinical characteristics and measures of quality of life data were obtained. In an attempt to understand the genetic architecture of the disease better, genome-wide single nucleotide polymorphism (SNP) genotype data were obtained, and a genome wide association study (GWAS) performed on 130 of the recruits. The analysis revealed genetic loci suggestively associated with the lipoedema phenotype, with further support provided by an independent cohort taken from the 100,000 Genomes Project. Top SNPs included loci associated with lipoma formation, biosynthesis of hormones and lipid hydroxylation. Exactly how these SNPs relate to a lipoedema disease mechanism is not yet understood but the findings are consistent with existing fat and hormone hypotheses. This first GWAS of a UK lipoedema cohort has identified genetic regions of suggestive association with the disease. Further replication of these findings in different populations is warranted.


2002 ◽  
Vol 41 (03) ◽  
pp. 191-195 ◽  
Author(s):  
Shigeaki Hinohara

SummaryIn this paper I mention the 19-year history of International Health Evaluation Association (IHEA) which was started in Washington D.C. by the great effort of Dr. G. Gilbert in Hawaii. In 1973 three regions were organized in this Association: 1) U.S.A., 2) Europe and 3) Pan-Pacific including Asia.I also mention the history of periodical health checkups in U.K., U.S.A. and Japan. In Japan it started in 1954, however, after adapting the system of Automated Multiphase Health Testing designed by the Kaiser Foundation of Auckland, Calif., in 1973, Japanese people paid much attention to this health screening system and the number of hospitals and clinics for health screening has increased tremendously and the number of examinees amounted to 2,875,449 in 2001.Finally, I conclude that IHEA should create a multi-disciplinary system to sustain a lifestyle with a high level of Quality of Life (QOL) for the people who really want to live fruitful lives by the successive health education.


2011 ◽  
Vol 16 (2) ◽  
pp. 104-110 ◽  
Author(s):  
Ingrid Lunt

The paper presents a brief history of the EuroPsy initiative which began in 1998 and is now in the process of implementation across European countries in the European Federation of Psychologists’ Associations (EFPA). EuroPsy defines a standard of professional education that aims to promote a high quality of education and professional practice for psychologists. The initiative was substantially supported by developments within the European Union (EU) and more widely in Europe, in particular the so-called Bologna process. This process, however, had a major political focus with an explicit commitment to facilitate mobility. Concerns for quality and a high level of professional education and an implied focus on consumer or client protection may not always sit easily with a commitment to facilitating professional mobility. This paper presents some of the challenges and potential tensions inherent in the EuroPsy.


Author(s):  
Taro Gilbert ◽  

SC Cuprom SA Bucharest Branch Baia Mare is known as one of the biggest copper factory from ores from Romania, but at the same time one of the biggest polluters from the recent history of the country. Placed in the Baia Mare basin, at the outskirts of the city, the plant generated, in the past, a significant negative impact over the environmental factors, especially over the air and soil. The monitoring of the environment factors in the period offunctioning and after closure revealed a high level of pollution of the emplacement. After ceasing of the activity, in 2009, the emplacement passed through a period of continuous degradation, successive demolitions of the buildings and minimum involving regarding the protection of the environmental factors and application of depollution processes. In this moment the platform of Cuprom Sa represents a tampon zone placed in the eastern part of Baia Mare, which stand in the path of development of the city in that direction due to the high level of degradation of the site, high level ofpollution and lack of capitalization measures.


Biology ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 934
Author(s):  
Babak J. Mehrara ◽  
Hyeung Ju Park ◽  
Raghu P. Kataru ◽  
Jacqueline Bromberg ◽  
Michelle Coriddi ◽  
...  

Recent studies suggest that Th2 cells play a key role in the pathology of secondary lymphedema by elaborating cytokines such as IL4 and IL13. The aim of this study was to test the efficacy of QBX258, a monoclonal IL4/IL13 neutralizing antibody, in women with breast cancer–related lymphedema (BCRL). We enrolled nine women with unilateral stage I/II BCRL and treated them once monthly with intravenous infusions of QBX258 for 4 months. We measured limb volumes, bioimpedance, and skin tonometry, and analyzed the quality of life (QOL) using a validated lymphedema questionnaire (Upper Limb Lymphedema 27, ULL-27) before treatment, immediately after treatment, and 4 months following treatment withdrawal. We also obtained 5 mm skin biopsies from the normal and lymphedematous limbs before and after treatment. Treatment was well-tolerated; however, one patient with a history of cellulitis developed cellulitis during the trial and was excluded from further analysis. We found no differences in limb volumes or bioimpedance measurements after drug treatment. However, QBX258 treatment improved skin stiffness (p < 0.001) and improved QOL measurements (Physical p < 0.05, Social p = 0.01). These improvements returned to baseline after treatment withdrawal. Histologically, treatment decreased epidermal thickness, the number of proliferating keratinocytes, type III collagen deposition, infiltration of mast cells, and the expression of Th2-inducing cytokines in the lymphedematous skin. Our limited study suggests that immunotherapy against Th2 cytokines may improve skin changes and QOL of women with BCRL. This treatment appears to be less effective for decreasing limb volumes; however, additional studies are needed.


2019 ◽  
Vol 93 (21) ◽  
Author(s):  
Camilla Patrizia Hrycak ◽  
Sonja Windmann ◽  
Wibke Bayer

ABSTRACT Adenovirus (AdV)-based vectors are popular experimental vaccine vectors, but despite their ability to induce strong immune responses, their application is impeded by widespread preexisting immunity against many AdV types that can impair or even abrogate the induction of transgene-specific immune responses. Therefore, the development of vectors based on AdV types with a low seroprevalence is important for effective AdV-based immunization in humans. We investigated the immunization efficacy of vectors based on AdV type 48 (Ad48) and Ad50 in the ovalbumin (ova) model as well as the Friend retrovirus (FV) model, which allows testing of the protective effect of vaccine-induced immunity. Using ova-encoding vectors, we found a significantly lower induction of ova-specific CD8+ T cells and antibody responses by Ad48- and Ad50-based vectors than by Ad5-based vectors. Similarly, we found a reduced induction of FV-specific CD8+ T cell responses in Ad48- and Ad50.Leader-Gag-immunized mice compared with that in Ad5-immunized mice; however, some of those mice were able to control the FV infection, and protection correlated with the level of neutralizing antibodies 10 days after FV challenge. Analyses of the AdV-specific antibodies and CD8+ T cells induced by the individual AdV types revealed a high level of cross-reactivity, and the efficacy of Ad48-based immunization was impaired in Ad5-preimmune mice. Our results show that the immunity induced by Ad48- and Ad50-based vectors is reduced compared to that induced by Ad5 and is sufficient to control FV infection in only some of the immunized mice. A high level of cross-reactivity suggests that AdV preimmunity must be considered even when applying rare AdV-based vectors. IMPORTANCE AdV-based vectors are important tools for the development of vaccines against a wide range of pathogens. While AdV vectors are generally considered safe and highly effective, their application can be severely impaired by preexisting immunity due to the widespread seroprevalence of some AdV types. The characterization of different AdV types with regard to immunogenicity and efficacy in challenge models is of great importance for the development of improved AdV-based vectors that allow for efficient immunization despite anti-AdV immunity. We show that the immunity induced by an Ad48-based vector is inferior to that induced by an Ad5-based vector but can still mediate the control of an FV infection in highly FV-susceptible mice. However, the efficacy of Ad48-based immunization was impaired in Ad5-preimmune mice. Importantly, we found cross-reactivity of both the humoral and cellular immune responses raised by the individual AdV types, suggesting that switching to a different AdV type may not be sufficient to circumvent preexisting anti-AdV immunity.


2020 ◽  
Vol 7 (5) ◽  
pp. 91-108
Author(s):  
M. S. Mosoyan ◽  
D. A. Fedorov

Today, robot-assisted surgery and the use of robots in medicine marks a qualitatively new stage in the development of minimally invasive technologies and endovideosurgery, due to the high level of accuracy, functionality and ergonomics of modern robotic systems. With the help of robotic technologies, the quality of diagnostic manipulations as well as the results of therapeutic procedures and surgical interventions are significantly improved, which ultimately leads to an improved prognosis and quality of life for patients, while also expanding the capabilities of clinicians. This review article presents the main historical milestones and prerequisites for the development of automation and robotic technologies used in various industries, from ancient times to the present. The history of the use of robotic procedures in various fields of medicine is briefly described. Special attention is paid to robot-assisted surgery as one of the main bases for applying modern technologies. At the moment, we can safely say that medical robotics plays a very important role in the development of surgery of the future.


2012 ◽  
Vol 19 (7) ◽  
pp. 1102-1109 ◽  
Author(s):  
Keyan Chen ◽  
Kui Zhao ◽  
Wenqi He ◽  
Wei Gao ◽  
Chuanbo Zhao ◽  
...  

ABSTRACTPorcine hemagglutinating encephalomyelitis (PHE) is caused by the coronavirus hemagglutinating encephalomyelitis virus (PHE-CoV), and the recent, rapid spread of PHE-CoV in piglets from many countries emphasizes the urgent need for a PHE-CoV vaccine. Here we use a murine model for evaluation of the induction of humoral and cellular immune responses by inactivated and PHE-CoV DNA vaccines in order to define the immune correlates for protection against PHE-CoV. The inactivated vaccine was composed of purified PHE-CoV and aluminum hydroxide gel (alum), which was chosen as an adjuvant because of its long history of safety for human use. The PHE-CoV DNA vaccine was constructed by subcloning the S1 gene of PHE-CoV into the pVAX1 vector to create the recombinant plasmid pV-S1. Our results showed that the inactivated PHE-CoV vaccine (IPV) elicited a high level of humoral immunity, resulting in good protection efficacy against PHE-CoV challenge. The IPV induced the IgG1 subclass of serum antibodies and expression of the cytokine interleukin-4 (IL-4), suggesting that the IPV generated a predominantly Th2-type immune response. The DNA vaccine was found to mediate primarily a cellular immune response with high levels of IgG2a and the cytokines IL-2 and gamma interferon (IFN-γ). However, mice that were vaccinated twice with the DNA vaccine and boosted with the IPV could mount a sufficient neutralizing antibody response against live PHE-CoV, with little variation in IgG1 and IgG2a levels, and showed high levels of IL-2 and IL-4. This response may activate both B and T cells to mount a specific humoral and cellular immune response that could, in turn, elicit a phagocyte-mediated defense against PHE-CoV infections to achieve viral clearance.


2021 ◽  
Author(s):  
Angelika Wagner ◽  
Erika Garner-Spitzer ◽  
Anna Margarita Schoetta ◽  
Maria Orola ◽  
Andrea Wessely ◽  
...  

Background Knowledge about humoral and cellular immunogenicity and their kinetics following SARS-CoV-2 mRNA vaccinations in immunosuppressed patients is limited. Methods Antibody and cytokine responses were assessed in 263 patients with either solid tumors (SOT, n=63), multiple myeloma (MM, n=70) or inflammatory bowel diseases (IBD, n=130) undergoing various immunosuppressive regimens and from 66 healthy controls before the first and the second, as well as four weeks and 5-6 months after the second mRNA vaccine dose with either BNT162b2 or mRNA-1273. Findings Four weeks after the second dose, seroconversion was lower in cancer than in IBD patients and controls, with the highest non-responder rate in MM patients (17.1%). S1-specific IgG levels correlated with neutralizing antibody titers. While antibody responses correlated with cellular responses in controls and IBD patients, IFN-g; and antibody responses did not in SOT and MM patients. At six months, 19.6% of patients with MM and 7.3% with SOT had become seronegative, while IBD patients and controls remained seropositive in 96.3% and 100%, respectively. Vaccinees receiving mRNA-1273 presented higher antibody levels than those vaccinated with BNT162b2. Interpretation Cancer patients may launch an inadequate seroresponse in the immediate time range following vaccination and up to six months, correlating with vaccine-specific cellular responses. These findings propose antibody testing in immunosuppressed - along with cellular testing - provides guidance for administration of additional vaccine doses, or may indicate the necessity for antibody treatment. IBD patients respond well to the vaccine, but treatment such as with TNF-a; inhibitors may reduce persistence of immune responses.


2018 ◽  
Vol 1 (80) ◽  
Author(s):  
Audrius Gocentas ◽  
Anatoli Landõr ◽  
Aleksandras Kriščiūnas

Research background and hypothesis. Replete schedule of competitions and intense training are features of contemporary team sports. Athletes, especially the most involved ones, may not have enough time to recover. As a consequence, aggregated fatigue can manifest in some undesirable form and affect athlete’s performance and health.Research aim. The aim of this study was to evaluate the changes in heart rate recovery (HRR) and investigate possible relations with sport-specifi c measures of effi cacy in professional basketball players during competition season.Research methods. Eight male high-level basketball players (mean ± SD, body mass, 97.3 ± 11.33 kg; height 2.02 ± 0.067 m, and age 23 ± 3.12 years) were investigated. The same basketball specifi c exercise was replicated several times from September till April during the practice sessions in order to assess the personal trends of HRR. Heart rate monitoring was performed using POLAR TEAM SYSTEM. Investigated athletes were ranked retrospectively according to the total amount of minutes played and the coeffi cients of effi cacy. Research results. There were signifi cant differences in the trends of HRR between the investigated players. The most effective players showed decreasing trends of HRR in all cases of ranking.Discussion and conclusions. Research fi ndings have shown that the quality of heart rate recovery differs between basketball players of the same team and could be associated with sport-specifi c effi cacy and competition playing time.Keywords: adaptation, autonomic control, monitoring training.


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