scholarly journals Nanobodies: Prospects of Expanding the Gamut of Neutralizing Antibodies Against the Novel Coronavirus, SARS-CoV-2

2020 ◽  
Vol 11 ◽  
Author(s):  
Rocktotpal Konwarh
Keyword(s):  
Neutralizing Antibodies ◽  
The Novel ◽  
Novel Coronavirus

scholarly journals Comparison of Four SARS-CoV-2 Neutralization Assays

Vaccines ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 13
Author(s):  
Lydia Riepler ◽  
Annika Rössler ◽  
Albert Falch ◽  
André Volland ◽  
Wegene Borena ◽  
...  
Keyword(s):  
Vesicular Stomatitis Virus ◽  
Neutralizing Antibodies ◽  
The Other ◽  
In Vitro Assays ◽  
The Novel ◽  
Effective Protection ◽  
Vaccine Candidates ◽  
Vesicular Stomatitis ◽  
Novel Coronavirus

Neutralizing antibodies are a major correlate of protection for many viruses including the novel coronavirus SARS-CoV-2. Thus, vaccine candidates should potently induce neutralizing antibodies to render effective protection from infection. A variety of in vitro assays for the detection of SARS-CoV-2 neutralizing antibodies has been described. However, validation of the different assays against each other is important to allow comparison of different studies. Here, we compared four different SARS-CoV-2 neutralization assays using the same set of patient samples. Two assays used replication competent SARS-CoV-2, a focus forming assay and a TCID50-based assay, while the other two assays used replication defective lentiviral or vesicular stomatitis virus (VSV)-based particles pseudotyped with SARS-CoV-2 spike. All assays were robust and produced highly reproducible neutralization titers. Titers of neutralizing antibodies correlated well between the different assays and with the titers of SARS-CoV-2 S-protein binding antibodies detected in an ELISA. Our study showed that commonly used SARS-CoV-2 neutralization assays are robust and that results obtained with different assays are comparable.

scholarly journals A Structural Landscape of Neutralizing Antibodies Against SARS-CoV-2 Receptor Binding Domain

2021 ◽  
Vol 12 ◽  
Author(s):  
Ling Niu ◽  
Kathryn N. Wittrock ◽  
Gage C. Clabaugh ◽  
Vikram Srivastava ◽  
Michael W. Cho
Keyword(s):  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Critical Role ◽  
Binding Domain ◽  
The Novel ◽  
Receptor Binding Domain ◽  
Correlates Of Protection ◽  
Immune Correlates ◽  
Virus Life Cycle ◽  
Novel Coronavirus

SARS-CoV-2, the novel coronavirus responsible for the ongoing COVID-19 pandemic, has been spreading rampantly. The global scientific community has responded rapidly to understand immune correlates of protection to develop vaccines and immunotherapeutics against the virus. The major goal of this mini review is to summarize current understanding of the structural landscape of neutralizing antibodies (nAbs) that target the receptor binding domain (RBD) of viral spike (S) glycoprotein. The RBD plays a critical role in the very first step of the virus life cycle. Better understanding of where and how nAbs bind the RBD should enable identification of sites of vulnerability and facilitate better vaccine design and formulation of immunotherapeutics. Towards this goal, we compiled 38 RBD-binding nAbs with known structures. Review of these nAb structures showed that (1) nAbs can be divided into five general clusters, (2) there are distinct non-neutralizing faces on the RBD, and (3) maximum of potentially four nAbs could bind the RBD simultaneously. Since most of these nAbs were isolated from virus-infected patients, additional analyses of vaccine-induced nAbs could facilitate development of improved vaccines.

scholarly journals The pigtail macaque (Macaca nemestrina) model of COVID-19 reproduces diverse clinical outcomes and reveals new and complex signatures of disease

2021 ◽  
Vol 17 (12) ◽  
pp. e1010162
Author(s):  
Alexandra Melton ◽  
Lara A. Doyle-Meyers ◽  
Robert V. Blair ◽  
Cecily Midkiff ◽  
Hunter J. Melton ◽  
...  
Keyword(s):  
T Cells ◽  
Neutralizing Antibodies ◽  
Severe Disease ◽  
Macaca Nemestrina ◽  
The Novel ◽  
Pigtail Macaque ◽  
Immunodeficiency Virus ◽  
Cytotoxic Molecules ◽  
Pathologic Lesions ◽  
Novel Coronavirus

The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 disease, has killed over five million people worldwide as of December 2021 with infections rising again due to the emergence of highly transmissible variants. Animal models that faithfully recapitulate human disease are critical for assessing SARS-CoV-2 viral and immune dynamics, for understanding mechanisms of disease, and for testing vaccines and therapeutics. Pigtail macaques (PTM, Macaca nemestrina) demonstrate a rapid and severe disease course when infected with simian immunodeficiency virus (SIV), including the development of severe cardiovascular symptoms that are pertinent to COVID-19 manifestations in humans. We thus proposed this species may likewise exhibit severe COVID-19 disease upon infection with SARS-CoV-2. Here, we extensively studied a cohort of SARS-CoV-2-infected PTM euthanized either 6- or 21-days after respiratory viral challenge. We show that PTM demonstrate largely mild-to-moderate COVID-19 disease. Pulmonary infiltrates were dominated by T cells, including CD4+ T cells that upregulate CD8 and express cytotoxic molecules, as well as virus-targeting T cells that were predominantly CD4+. We also noted increases in inflammatory and coagulation markers in blood, pulmonary pathologic lesions, and the development of neutralizing antibodies. Together, our data demonstrate that SARS-CoV-2 infection of PTM recapitulates important features of COVID-19 and reveals new immune and viral dynamics and thus may serve as a useful animal model for studying pathogenesis and testing vaccines and therapeutics.

scholarly journals Mutations in SARS-CoV-2 Variants Modulate the Microscopic Dynamics of Neutralizing Antibodies

2021 ◽  
Author(s):  
Dhiman Ray ◽  
Riley Nicolas Quijano ◽  
Ioan Andricioaei
Keyword(s):  
Monoclonal Antibodies ◽  
Neutralizing Antibodies ◽  
Rational Design ◽  
Graph Connectivity ◽  
World Population ◽  
The Novel ◽  
Long Distance ◽  
Correlated Motion ◽  
Novel Coronavirus ◽  
Microscopic Dynamics

Monoclonal antibodies have emerged as viable treatment for the COVID-19 disease caused by the SARS-CoV-2 virus. But the new viral variants can reduce the efficacy of the currently available antibodies, as well as diminish the vaccine induced immunity. Here, we demonstrate how the microscopic dynamics of the SARS-CoV-2 neutralizing monoclonal antibodies, can be modulated by the mutations present in the spike proteins of the variants currently circulating in the world population. We show that the dynamical perturbation in the antibody structure can be diverse, depending both on the nature of the antibody and on the location of the mutation. The correlated motion between the antibody and the receptor binding domain (RBD) can also be changed, altering the binding affinity. By constructing a protein graph connectivity network, we could delineate the mutant induced modifications in the allosteric information flow pathway through the antibody, and observed the presence of both localized and long distance effects. We identified a loop consisting of residues 470-490 in the RBD which works like an anchor preventing the detachment of the antibodies, and individual mutations in that region can significantly affect the antibody binding propensity. Our study provides fundamental and atomistically detailed insight on how virus neutralization by monoclonal antibody can be impacted by the mutations in the epitope, and can potentially facilitate the rational design of monoclonal antibodies, effective against the new variants of the novel coronavirus.

scholarly journals The emergence of SARS-CoV-2 variants threatens to decrease the efficacy of neutralizing antibodies and vaccines

2021 ◽  
Author(s):  
Kensaku Murano ◽  
Youjia Guo ◽  
Haruhiko Siomi
Keyword(s):  
Monoclonal Antibodies ◽  
Severe Acute Respiratory Syndrome ◽  
Neutralizing Antibodies ◽  
The Novel ◽  
Therapeutic Antibodies ◽  
Human Origin ◽  
New Challenges ◽  
Novel Coronavirus

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the coronavirus disease (COVID-19) pandemic. As of August 2021, more than 200 million people have been infected with the virus and 4.3 million have lost their lives. Various monoclonal antibodies of human origin that neutralize the SARS-CoV-2 infection have been isolated from convalescent patients for therapeutic and prophylactic purposes. Several vaccines have been developed to restrict the spread of the virus and have been rapidly administered. However, the rollout of vaccines has coincided with the spread of variants of concern. Emerging variants of SARS-CoV-2 present new challenges for therapeutic antibodies and threaten the efficacy of current vaccines. Here, we review the problems faced by neutralizing antibodies and vaccines in the midst of the increasing spread of mutant viruses.

scholarly journals Retrospective analysis of 426 donors of a convalescent collective after mild COVID-19

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0247665
Author(s):  
Tobias Flieder ◽  
Tanja Vollmer ◽  
Benjamin Müller ◽  
Jens Dreier ◽  
Bastian Fischer ◽  
...  
Keyword(s):  
Detection Limit ◽  
Neutralizing Antibodies ◽  
Virus Detection ◽  
The Novel ◽  
Igg Antibodies ◽  
Rt Pcr ◽  
Future Studies ◽  
The World ◽  
Iga Antibodies ◽  
Novel Coronavirus

Background The novel coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread across the world. The aim of our study was to characterize mild courses and to determine the antibody status for these patients. Methods We initiated an appeal for convalescent plasma donations. 615 people contacted us, and we ultimately included 426 in our analyses, in whom it was possible to assume COVID-19 based on detection of specific SARS-CoV-2 antibodies or virus detection during the disease using RT-PCR. Results The median duration of the disease was 12 days and the most common symptoms were fatigue, cough and olfactory and gustatory dysfunction. Anti-SARS-CoV-2 IgG was detected in 82.4% of the persons and IgA antibodies were found in 73.9%. In 10.8%, no antibodies were detectable despite a positive RT-PCR result during the disease. Nevertheless, of 24 persons with asymptomatic courses of COVID-19, antibodies against SARS-CoV-2 could be detected in 23 (96%). Furthermore, there was a correlation between the duration of the disease and the detection of IgG antibodies. In addition, a correlation between the determined IgG antibodies and neutralizing antibodies was shown. Conclusion In this study, we were able to describe mild COVID-19 courses and determine antibody statuses for them. It could be shown that, despite SARS-CoV-2 detection during the disease, not all individuals developed antibodies or their level of antibodies had dropped below the detection limit shortly after the end of the disease. The extent to which immunity to re-infection is given in persons with undetectable antibodies (IgG, IgA) needs to be investigated in future studies.

scholarly journals Design of SARS-CoV-2 RBD mRNA Vaccine Using Novel Ionizable Lipids

2020 ◽  
Author(s):  
Uri Elia ◽  
Srinivas Ramishetti ◽  
Niels Dammes ◽  
Erez Bar-Haim ◽  
Gonna Somu Naidu ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Cellular Response ◽  
Humoral Response ◽  
The Novel ◽  
Receptor Binding Domain ◽  
A Cell ◽  
Luciferase Mrna ◽  
Novel Coronavirus ◽  
High Level

AbstractThe novel coronavirus SARS-CoV-2 has been identified as the causal agent of COVID-19 and stands at the center of the current global human pandemic, with death toll exceeding one million. The urgent need for a vaccine has led to the development of various immunization approaches. mRNA vaccines represent a cell-free, simple and rapid platform for immunization, and therefore have been employed in recent studies towards the development of a SARS-CoV-2 vaccine. In this study, we present the design of a lipid nanoparticles (LNP)-encapsulated receptor binding domain (RBD) mRNA vaccine. Several ionizable lipids have been evaluated in vivo in a luciferase mRNA reporter assay, and two leading LNPs formulation have been chosen for the subsequent RBD mRNA vaccine experiment. Intramuscular administration of LNP RBD mRNA elicited robust humoral response, high level of neutralizing antibodies and a Th1-biased cellular response in BALB/c mice. These novel lipids open new avenues for mRNA vaccines in general and for a COVID19 vaccine in particular.

scholarly journals A SARS-CoV-2-ellenes antitestekkel végzett terápia helye a COVID–19 kezelésében

2021 ◽  
Vol 162 (51) ◽  
pp. 2030-2039
Keyword(s):  
Clinical Trial ◽  
High Risk ◽  
Healthcare System ◽  
Neutralizing Antibodies ◽  
Therapeutic Option ◽  
Passive Immunization ◽  
Published Data ◽  
The Novel ◽  
Novel Coronavirus ◽  
Made In

Összefoglaló. Az új típusú koronavírus (SARS-CoV-2) okozta fertőzés és a COVID–19 elleni küzdelem egyik lehetősége a SARS-CoV-2-ellenes neutralizáló antitestekkel végzett passzív immunizáció. Az utóbbi időben számos készítmény jutott el a klinikai kipróbálásig. Az alábbiakban áttekintjük ezen készítmények legfőbb tulajdonságait és az antitest-terápiával elért klinikai eredményeket. Ezek alapján elsősorban prehospitálisan, az állapotprogresszió szempontjából leginkább veszélyeztetett populációnál alkalmazva, e készítmények jelentősen csökkenthetik az állapotromlás esélyét és a kórházi ellátás igényét, ezáltal javíthatják a kimenetelt, és mérsékelhetik az egészségügyi ellátórendszer terhelését. Orv Hetil. 2021; 162(51): 2030–2039. Summary. Passive immunization is a therapeutic option in the fight against the infection caused by the novel coronavirus (SARS-CoV-2) and COVID-19. Significant advances have been made in the development of SARS-CoV-2 neutralizing antibodies. Here we discuss the antibodies under clinical trial and the published data regarding their clinical efficacy. Based on these, when given to non-hospitalized patients at high risk for disease progression, these antibodies can significantly reduce worsening of the disease and the need for hospitalization. This can improve the outcomes of patients and help reduce the burden on the healthcare system. Orv Hetil. 2021; 162(51): 2030–2039.

scholarly journals The pigtail macaque (Macaca nemestrina) model of COVID-19 reproduces diverse clinical outcomes and reveals new and complex signatures of disease

2021 ◽  
Author(s):  
Alexandra Melton ◽  
Lara A Doyle-Meyers ◽  
Robert V Blair ◽  
Cecily Midkiff ◽  
Hunter J Melton ◽  
...  
Keyword(s):  
T Cells ◽  
Neutralizing Antibodies ◽  
Severe Disease ◽  
Macaca Nemestrina ◽  
The Novel ◽  
Pigtail Macaque ◽  
Immunodeficiency Virus ◽  
Cytotoxic Molecules ◽  
Pathologic Lesions ◽  
Novel Coronavirus

The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 disease, has killed over four million people worldwide as of July 2021 with infections rising again due to the emergence of highly transmissible variants. Animal models that faithfully recapitulate human disease are critical for assessing SARS-CoV-2 viral and immune dynamics, for understanding mechanisms of disease, and for testing vaccines and therapeutics. Pigtail macaques (PTM, Macaca nemestrina) demonstrate a rapid and severe disease course when infected with simian immunodeficiency virus (SIV), including the development of severe cardiovascular symptoms that are pertinent to COVID-19 manifestations in humans. We thus proposed this species may likewise exhibit severe COVID-19 disease upon infection with SARS-CoV-2. Here, we extensively studied a cohort of SARS-CoV-2-infected PTM euthanized either 6- or 21-days after respiratory viral challenge. We show that PTM demonstrate largely mild-to-moderate COVID-19 disease. Pulmonary infiltrates were dominated by T cells, including CD4+ T cells that upregulate CD8 and express cytotoxic molecules, as well as virus-targeting T cells that were predominantly CD4+. We also noted increases in inflammatory and coagulation markers in blood, pulmonary pathologic lesions, and the development of neutralizing antibodies. Together, our data demonstrate that SARS-CoV-2 infection of PTM recapitulates important features of COVID-19 and reveals new immune and viral dynamics and thus may serve as a useful animal model for studying pathogenesis and testing vaccines and therapeutics.

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