scholarly journals Potent SARS-CoV-2 neutralizing antibodies selected from a human antibody library constructed decades ago

2020 ◽  
Author(s):  
Min Qiang ◽  
Peixiang Ma ◽  
Yu Li ◽  
Hejun Liu ◽  
Adam Harding ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Somatic Hypermutation ◽  
Human Antibody ◽  
Antibody Library ◽  
Origin And Evolution ◽  
The Public ◽  
History Of ◽  
Antibody Discovery ◽  
Antibody Libraries ◽  
Public Health Challenge

ABSTRACTCombinatorial antibody libraries not only effectively reduce antibody discovery to a numbers game, but enable documentation of the history of antibody responses in an individual. The SARS-CoV-2 pandemic has prompted a wider application of this technology to meet the public health challenge of pandemic threats in the modern era. Herein, we used a combinatorial human antibody library constructed 20 years before the COVID-19 pandemic to discover three highly potent antibodies that selectively bind SARS-CoV-2 spike protein and neutralize authentic SARS-CoV-2 virus. Compared to neutralizing antibodies from COVID-19 patients with generally low somatic hypermutation (SHM), these antibodies contain over 13-22 SHMs, many of which are involved in specific interactions in crystal structures with SARS-CoV-2 spike RBD. The identification of these somatically mutated antibodies in a pre-pandemic library raises intriguing questions about the origin and evolution of human immune responses to SARS-CoV-2.

scholarly journals Vaccine-Associated Disease Enhancement (VADE): Considerations in Postvaccination COVID-19

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Rahajeng N. Tunjungputri ◽  
Erpryta Nurdia Tetrasiwi ◽  
Merlinda Veronica ◽  
Jacub Pandelaki ◽  
Fera Ibrahim ◽  
...  
Keyword(s):  
Decision Making ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Vaccine Uptake ◽  
The Public ◽  
True Incidence ◽  
Mass Immunization ◽  
History Of ◽  
New Phase

Introduction. The COVID-19 pandemic has entered a new phase with the roll-out of several vaccines worldwide at an accelerated phase. The occurrence of a more severe presentation of COVID-19 after vaccination may affect policymakers’ decision-making and vaccine uptake by the public. Vaccine-associated disease enhancement (VADE) is the modified presentation of infections in individuals after having received a prior vaccination. Currently, little is known about the potential of vaccine-associated disease enhancement (VADE) following COVID-19 immunization. Case Illustration. We herewith report two patients admitted with confirmed COVID-19 pneumonia with a history of CoronaVac vaccination. The first patient with a relatively milder course of the disease had received two doses of CoronaVac, whereas the second patient with a more progressive course of the disease received only one dose before developing symptoms and being admitted to the hospital. Our observations suggest that vaccination could act in boosting the inflammatory process and reveal the previously asymptomatic COVID-19 illness. Theoretically, vaccines could induce VADE, where only suboptimal, nonprotective titers of neutralizing antibodies were produced or proinflammatory T-helper type 2 response was induced. Secondly, enhanced respiratory disease (ERD) could manifest, where pulmonary symptoms are more severe due to peribronchial monocytic and eosinophilic infiltration. Understanding VADE is important for the decision-making by the public, clinicians, and policymakers and is warranted for successful vaccination uptake. Conclusion. We report two cases of patients developing COVID-19 shortly after CoronaVac vaccination in which VADE is likely. We recommend that current vaccination strategies consider the measurement of neutralizing antibody titer as a guide in ensuring the safest strategy for mass immunization. Studies are needed to investigate the true incidence of VADE on vaccinated individuals as well as on how to differentiate between VADE and severe manifestations of COVID-19 that are unrelated to vaccination.

scholarly journals Neutralizing Antibodies to SARS‐CoV‐2 Selected from a Human Antibody Library Constructed Decades Ago

2021 ◽  
pp. 2102181
Author(s):  
Min Qiang ◽  
Peixiang Ma ◽  
Yu Li ◽  
Hejun Liu ◽  
Adam Harding ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Human Antibody ◽  
Antibody Library

scholarly journals Functional selection of protease inhibitory antibodies

2019 ◽  
Vol 116 (33) ◽  
pp. 16314-16319 ◽  
Author(s):  
Tyler Lopez ◽  
Zahid Mustafa ◽  
Chuan Chen ◽  
Ki Baek Lee ◽  
Aaron Ramirez ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Peptide Sequence ◽  
Great Promise ◽  
Human Antibody ◽  
Cellular Assays ◽  
Antibody Discovery ◽  
Antibody Libraries ◽  
Inhibitory Antibodies ◽  
Cleavable Peptide ◽  
Inhibition Potency

Critical for diverse biological processes, proteases represent one of the largest families of pharmaceutical targets. To inhibit pathogenic proteases with desired selectivity, monoclonal antibodies (mAbs) hold great promise as research tools and therapeutic agents. However, identification of mAbs with inhibitory functions is challenging because current antibody discovery methods rely on binding rather than inhibition. This study developed a highly efficient selection method for protease inhibitory mAbs by coexpressing 3 recombinant proteins in the periplasmic space of Escherichia coli—an antibody clone, a protease of interest, and a β-lactamase modified by insertion of a protease cleavable peptide sequence. During functional selection, inhibitory antibodies prevent the protease from cleaving the modified β-lactamase, thereby allowing the cell to survive in the presence of ampicillin. Using this method to select from synthetic human antibody libraries, we isolated panels of mAbs inhibiting 5 targets of 4 main protease classes: matrix metalloproteinases (MMP-14, a predominant target in metastasis; MMP-9, in neuropathic pain), β-secretase 1 (BACE-1, an aspartic protease in Alzheimer’s disease), cathepsin B (a cysteine protease in cancer), and Alp2 (a serine protease in aspergillosis). Notably, 37 of 41 identified binders were inhibitory. Isolated mAb inhibitors exhibited nanomolar potency, exclusive selectivity, excellent proteolytic stability, and desired biological functions. Particularly, anti-Alp2 Fab A4A1 had a binding affinity of 11 nM and inhibition potency of 14 nM, anti-BACE1 IgG B2B2 reduced amyloid beta (Aβ40) production by 80% in cellular assays, and IgG L13 inhibited MMP-9 but not MMP-2/-12/-14 and significantly relieved neuropathic pain development in mice.

From the History of the Public Library in the Village Tagai of Simbirsk District in Simbirsk Province

2010 ◽  
pp. 102-106
Author(s):  
Valentina M. Patutkina
Keyword(s):  
Public Library ◽  
Library History ◽  
The Public ◽  
Ulyanovsk Region ◽  
History Of ◽  
In The Beginning ◽  
The Village

The article is dedicated to unknown page in the library history of Ulyanovsk region. The author writes about the role of Trusteeship on people temperance in opening of libraries. The history of public library organized in the beginning of XX century in the Tagai village of Simbirsk district in Simbirsk province is renewed.

The Challenges in Dealing with Organized Crime and its Consequences in Modern Societies in Albania, Kosovo and Macedonia – the Balkan Peninsula

2015 ◽  
Vol 5 (1) ◽  
pp. 161
Author(s):  
Bashkim Selmani ◽  
Bekim Maksuti
Keyword(s):  
Organized Crime ◽  
Balkan Peninsula ◽  
Human Mind ◽  
Negative Consequences ◽  
The Public ◽  
Before And After ◽  
History Of ◽  
European Standards ◽  
Organized Crime Groups ◽  
Further Development

The profound changes within the Albanian society, including Albania, Kosovo and Macedonia, before and after they proclaimed independence (in exception of Albania), with the establishment of the parliamentary system resulted in mass spread social negative consequences such as crime, drugs, prostitution, child beggars on the street etc. As a result of these occurred circumstances emerged a substantial need for changes within the legal system in order to meet and achieve the European standards or behaviors and the need for adoption of many laws imported from abroad, but without actually reading the factual situation of the psycho-economic position of the citizens and the consequences of the peoples’ occupations without proper compensation, as a remedy for the victims of war or peace in these countries. The sad truth is that the perpetrators not only weren’t sanctioned, but these regions remained an untouched haven for further development of criminal activities, be it from the public state officials through property privatization or in the private field. The organized crime groups, almost in all cases, are perceived by the human mind as “Mafia” and it is a fact that this cannot be denied easily. The widely spread term “Mafia” is mostly known around the world to define criminal organizations.The Balkan Peninsula is highly involved in these illegal groups of organized crime whose practice of criminal activities is largely extended through the Balkan countries such as Kosovo, Albania, Macedonia, Serbia, Bosnia, Croatia, Montenegro, etc. Many factors contributed to these strategic countries to be part of these types of activities. In general, some of the countries have been affected more specifically, but in all of the abovementioned countries organized crime has affected all areas of life, leaving a black mark in the history of these states.

La valorisation des prestations non-bois: particularités genevoises (essai) | Commercialization of non-wood forest services: the case of Geneva (essay)

2009 ◽  
Vol 160 (8) ◽  
pp. 232-234
Author(s):  
Patrik Fouvy
Keyword(s):  
Forest Regeneration ◽  
Biological Diversity ◽  
The State ◽  
Forest Land ◽  
Private Forests ◽  
The Public ◽  
Public Body ◽  
Provision Of Services ◽  
History Of ◽  
Near Future

The history of the forests in canton Geneva, having led to these being disconnected from productive functions, provides a symptomatic demonstration that the services provided by the forest eco-system are common goods. Having no hope of financial returns in the near future and faced with increasing social demands, the state has invested in the purchase of forest land, financed projects for forest regeneration and improvement of biological diversity and developed infrastructures for visitors. In doing this the state as a public body takes on the provision of services in the public interest. But the further funding for this and for expenses for the private forests, which must be taken into account, are not secured for the future.

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