scholarly journals Cross-Reactive Immune Responses toward the Common Cold Human Coronaviruses and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): Mini-Review and a Murine Study

2021 ◽  
Vol 9 (8) ◽  
pp. 1643
Author(s):  
Robert E. Sealy ◽  
Julia L. Hurwitz
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Immune Responses ◽  
Common Cold ◽  
Small Animal ◽  
Specific Antibodies ◽  
The United Kingdom ◽  
Small Animal Models ◽  
Human Coronaviruses ◽  
Human Infections ◽  
Experimental Challenge

While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes serious morbidity and mortality in humans (coronavirus disease 2019, COVID-19), there is an enormous range of disease outcomes following virus exposures. Some individuals are asymptomatic while others succumb to virus infection within days. Presently, the factors responsible for disease severity are not fully understood. One factor that may influence virus control is pre-existing immunity conferred by an individual’s past exposures to common cold human coronaviruses (HCoVs). Here, we describe previous literature and a new, murine study designed to examine cross-reactive immune responses between SARS-CoV-2 and common cold HCoVs (represented by prototypes OC43, HKU1, 229E, and NL63). Experimental results have been mixed. In SARS-CoV-2-unexposed humans, cross-reactive serum antibodies were identified toward nucleocapsid (N) and the spike subunit S2. S2-specific antibodies were in some cases associated with neutralization. SARS-CoV-2-unexposed humans rarely exhibited antibody responses to the SARS-CoV-2 spike subunit S1, and when naïve mice were immunized with adjuvanted S1 from either SARS-CoV-2 or common cold HCoVs, S1-specific antibodies were poorly cross-reactive. When humans were naturally infected with SARS-CoV-2, cross-reactive antibodies that recognized common cold HCoV antigens increased in magnitude. Cross-reactive T cells, like antibodies, were present in humans prior to SARS-CoV-2 exposures and increased following SARS-CoV-2 infections. Some studies suggested that human infections with common cold HCoVs afforded protection against disease caused by subsequent exposures to SARS-CoV-2. Small animal models are now available for the testing of controlled SARS-CoV-2 infections. Additionally, in the United Kingdom, a program of SARS-CoV-2 human challenge experiments has received regulatory approval. Future, controlled experimental challenge studies may better define how pre-existing, cross-reactive immune responses influence SARS-CoV-2 infection outcomes.

scholarly journals Immunological characteristics govern the transition of COVID-19 to endemicity

Science ◽  
2021 ◽  
Vol 371 (6530) ◽  
pp. 741-745 ◽  
Author(s):  
Jennie S. Lavine ◽  
Ottar N. Bjornstad ◽  
Rustom Antia
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Common Cold ◽  
Severe Disease ◽  
Epidemiological Data ◽  
Benign Nature ◽  
The Common ◽  
Human Coronaviruses ◽  
Pandemic Vaccine

We are currently faced with the question of how the severity of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may change in the years ahead. Our analysis of immunological and epidemiological data on endemic human coronaviruses (HCoVs) shows that infection-blocking immunity wanes rapidly but that disease-reducing immunity is long-lived. Our model, incorporating these components of immunity, recapitulates both the current severity of SARS-CoV-2 infection and the benign nature of HCoVs, suggesting that once the endemic phase is reached and primary exposure is in childhood, SARS-CoV-2 may be no more virulent than the common cold. We predict a different outcome for an emergent coronavirus that causes severe disease in children. These results reinforce the importance of behavioral containment during pandemic vaccine rollout, while prompting us to evaluate scenarios for continuing vaccination in the endemic phase.

scholarly journals SARS-CoV-2 infections elicit higher levels of original antigenic sin antibodies compared to SARS-CoV-2 mRNA vaccinations

2021 ◽  
Author(s):  
Elizabeth M. Anderson ◽  
Theresa Eilola ◽  
Eileen Goodwin ◽  
Marcus J. Bolton ◽  
Sigrid Gouma ◽  
...  
Keyword(s):  
Health Care ◽  
Severe Acute Respiratory Syndrome ◽  
Health Care Workers ◽  
Magnetic Bead ◽  
Antibody Responses ◽  
List Type ◽  
Specific Antibodies ◽  
Care Workers ◽  
Human Coronaviruses ◽  
Original Antigenic Sin

SUMMARYSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines elicit higher levels of antibodies compared to natural SARS-CoV-2 infections in most individuals; however, the specificities of antibodies elicited by vaccination versus infection remain incompletely understood. Here, we characterized the magnitude and specificity of SARS-CoV-2 spike-reactive antibodies from 10 acutely infected health care workers and 23 participants who received mRNA-based SARS-CoV-2 vaccines. We found that infection and primary mRNA vaccination elicited S1 and S2-reactive antibodies, while secondary vaccination boosted mostly S1 antibodies. Using magnetic bead-based absorption assays, we found that SARS-CoV-2 infections elicited a large proportion of original antigenic sin-like antibodies that bound efficiently to common seasonal human coronaviruses but poorly to SARS-CoV-2. In converse, vaccination only modestly boosted antibodies reactive to common seasonal human coronaviruses and these antibodies bound efficiently to SARS-CoV-2. Our data indicate that SARS-CoV-2 mRNA vaccinations elicit fundamentally different antibody responses compared to SARS-CoV-2 infections.Abstract FigureHIGHLIGHTSSARS-CoV-2 mRNA vaccines elicit higher levels of antibodies compared to SARS-CoV-2 infectionsThe first dose of an mRNA vaccine generates both S1 and S2 responses while the second dose boosts primarily S1-specific antibodiesSARS-CoV-2 infections, but not mRNA vaccinations, elicit high levels of antibodies that bind strongly to seasonal coronaviruses but weakly to SARS-CoV-2

scholarly journals Multiplex qPCR discriminates variants of concern to enhance global surveillance of SARS-CoV-2

PLoS Biology ◽  
2021 ◽  
Vol 19 (5) ◽  
pp. e3001236
Author(s):  
Chantal B. F. Vogels ◽  
Mallery I. Breban ◽  
Isabel M. Ott ◽  
Tara Alpert ◽  
Mary E. Petrone ◽  
...  
Keyword(s):  
South Africa ◽  
United Kingdom ◽  
Severe Acute Respiratory Syndrome ◽  
Immune Responses ◽  
Primary Target ◽  
Pcr Assay ◽  
Gene Target ◽  
Spike Gene ◽  
The United Kingdom ◽  
The World

With the emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants that may increase transmissibility and/or cause escape from immune responses, there is an urgent need for the targeted surveillance of circulating lineages. It was found that the B.1.1.7 (also 501Y.V1) variant, first detected in the United Kingdom, could be serendipitously detected by the Thermo Fisher TaqPath Coronavirus Disease 2019 (COVID-19) PCR assay because a key deletion in these viruses, spike Δ69–70, would cause a “spike gene target failure” (SGTF) result. However, a SGTF result is not definitive for B.1.1.7, and this assay cannot detect other variants of concern (VOC) that lack spike Δ69–70, such as B.1.351 (also 501Y.V2), detected in South Africa, and P.1 (also 501Y.V3), recently detected in Brazil. We identified a deletion in the ORF1a gene (ORF1a Δ3675–3677) in all 3 variants, which has not yet been widely detected in other SARS-CoV-2 lineages. Using ORF1a Δ3675–3677 as the primary target and spike Δ69–70 to differentiate, we designed and validated an open-source PCR assay to detect SARS-CoV-2 VOC. Our assay can be rapidly deployed in laboratories around the world to enhance surveillance for the local emergence and spread of B.1.1.7, B.1.351, and P.1.

scholarly journals The human coronaviruses (HCoVs) and the molecular mechanisms of SARS-CoV-2 infection

2020 ◽  
Vol 99 (1) ◽  
pp. 93-106
Author(s):  
Luigi Santacroce ◽  
Ioannis A. Charitos ◽  
Domenico M. Carretta ◽  
Emanuele De Nitto ◽  
Roberto Lovero
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Respiratory Tract ◽  
Common Cold ◽  
Molecular Mechanisms ◽  
Middle Eastern ◽  
International Committee ◽  
Upper Respiratory Tract ◽  
Human Coronaviruses ◽  
The 1960S ◽  
Tract Infections

AbstractIn humans, coronaviruses can cause infections of the respiratory system, with damage of varying severity depending on the virus examined: ranging from mild-to-moderate upper respiratory tract diseases, such as the common cold, pneumonia, severe acute respiratory syndrome, kidney failure, and even death. Human coronaviruses known to date, common throughout the world, are seven. The most common—and least harmful—ones were discovered in the 1960s and cause a common cold. Others, more dangerous, identified in the early 2000s and cause more severe respiratory tract infections. Among these the SARS-CoV, isolated in 2003 and responsible for the severe acute respiratory syndrome (the so-called SARS), which appeared in China in November 2002, the coronavirus 2012 (2012-nCoV) cause of the Middle Eastern respiratory syndrome (MERS) from coronavirus, which exploded in June 2012 in Saudi Arabia, and actually SARS-CoV-2. On December 31, 2019, a new coronavirus strain was reported in Wuhan, China, identified as a new coronavirus beta strain ß-CoV from group 2B, with a genetic similarity of approximately 70% to SARS-CoV, the virus responsible of SARS. In the first half of February, the International Committee on Taxonomy of Viruses (ICTV), in charge of the designation and naming of the viruses (i.e., species, genus, family, etc.), thus definitively named the new coronavirus as SARS-CoV-2. This article highlights the main knowledge we have about the biomolecular and pathophysiologic mechanisms of SARS-CoV-2.

scholarly journals The Human Coronaviruses (HCoVs) and the Molecular Mechanisms of SARS-CoV-2 Infection

2020 ◽  
Author(s):  
Luigi Santacroce ◽  
Ioannis A. Charitos ◽  
Domenico M. Carretta ◽  
Emanuele De Nitto ◽  
Roberto Lovero
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Respiratory Tract ◽  
Common Cold ◽  
Molecular Mechanisms ◽  
Middle Eastern ◽  
International Committee ◽  
Upper Respiratory Tract ◽  
Human Coronaviruses ◽  
The 1960S ◽  
Tract Infections

In humans, coronaviruses can cause infections of the respiratory system, with damage of varying severity depending on the virus examined: ranging from mild or moderate upper respiratory tract diseases, such as the common cold, to pneumonia, severe acute respiratory syndrome, kidney failure and even death. Human coronaviruses known to date, common throughout the world, are seven. The most common - and least harmful - ones were discovered in the 1960s and cause a common cold. Others, more dangerous, were identified in the early 2000s and cause more severe respiratory tract infections. Among these the SARS-CoV, isolated in 2003 and responsible for the Severe Acute Respiratory Syndrome (the so-called SARS), which appeared in China in November 2002, the Coronavirus 2012 (2012-nCoV) cause of the Middle Eastern Respiratory Syndrome from Coronavirus (MERS), which exploded in June 2012 in Saudi Arabia, and actually SARS-CoV-2. On December 31, 2019, a new Coronavirus strain was reported in Wuhan, China, identified as a new Coronavirus beta strain ß-CoV from Group 2B, with a genetic similarity of approximately 70% to SARS-CoV, the virus responsible. of SARS. In the first half of February, the International Committee on Taxonomy of Viruses (ICTV), in charge of the designation and naming of the viruses (i.e., species, genus, family, etc.), thus definitively named the new coronavirus as SARS-CoV-2. This article highlights the main knowledge we have about the biomolecular and pathophysiologic mechanisms of SARS-CoV-2.

scholarly journals Rationally repurposed nitroxoline inhibits preclinical models of Epstein–Barr virus-associated lymphoproliferation

2021 ◽  
Author(s):  
Maite Ibáñez de Garayo ◽  
Wendi Liu ◽  
Nicole C. Rondeau ◽  
Christopher B. Damoci ◽  
JJ L. Miranda
Keyword(s):  
Epstein Barr Virus ◽  
Small Animal ◽  
Preclinical Models ◽  
Bet Inhibitor ◽  
Barr Virus ◽  
Chelating Activity ◽  
Metal Chelating ◽  
Small Animal Models ◽  
Epstein Barr ◽  
Tract Infections

AbstractRepurposing of currently used drugs for new indications benefits from known experience with those agents. Rational repurposing can be achieved when newly uncovered molecular activities are leveraged against diseases that utilize those mechanisms. Nitroxoline is an antibiotic with metal-chelating activity used to treat urinary tract infections. This small molecule also inhibits the function of bromodomain and extraterminal (BET) proteins that regulate oncogene expression in cancer. Lymphoproliferation driven by the Epstein–Barr virus (EBV) depends on these same proteins. We therefore tested the efficacy of nitroxoline against cell culture and small animal models of EBV-associated lymphoproliferation. Nitroxoline indeed reduces cell and tumor growth. Nitroxoline also acts faster than the prototype BET inhibitor JQ1. We suggest that this rational repurposing may hold translational promise.

scholarly journals History of IgA Nephropathy Mouse Models

2021 ◽  
Vol 10 (14) ◽  
pp. 3142
Author(s):  
Batoul Wehbi ◽  
Virginie Pascal ◽  
Lina Zawil ◽  
Michel Cogné ◽  
Jean-Claude Aldigier
Keyword(s):  
Iga Nephropathy ◽  
Small Animal ◽  
Experimental Models ◽  
Murine Models ◽  
Therapeutic Approaches ◽  
Complement Components ◽  
Simple Description ◽  
Primary Glomerulonephritis ◽  
History Of ◽  
Small Animal Models

IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the world. It was first described in 1968 by Jean Berger and Nicole Hinglais as the presence of intercapillary deposits of IgA. Despite this simple description, patients with IgAN may present very broad clinical features ranging from the isolated presence of IgA in the mesangium without clinical or biological manifestations to rapidly progressive kidney failure. These features are associated with a variety of histological lesions, from the discrete thickening of the mesangial matrix to diffuse cell proliferation. Immunofluorescence on IgAN kidney specimens shows the isolated presence of IgA or its inconsistent association with IgG and complement components. This clinical heterogeneity of IgAN clearly echoes its complex and multifactorial pathophysiology in humans, inviting further analyses of its various aspects through the use of experimental models. Small-animal models of IgAN provide the most pertinent strategies for studying the multifactorial aspects of IgAN pathogenesis and progression. Although only primates have the IgA1 subclass, several murine models have been developed in which various aspects of immune responses are deregulated and which are useful in the understanding of IgAN physiopathology as well as in the assessment of IgAN therapeutic approaches. In this manuscript, we review all murine IgAN models developed since 1968 and discuss their remarkable contribution to understanding the disease.

scholarly journals SARS-CoV-2 within-host diversity and transmission

Science ◽  
2021 ◽  
Vol 372 (6539) ◽  
pp. eabg0821 ◽  
Author(s):  
Katrina A. Lythgoe ◽  
Matthew Hall ◽  
Luca Ferretti ◽  
Mariateresa de Cesare ◽  
George MacIntyre-Cockett ◽  
...  
Keyword(s):  
United Kingdom ◽  
Severe Acute Respiratory Syndrome ◽  
Phylogenetic Tree ◽  
Immune Escape ◽  
Clinical Samples ◽  
Diversity Patterns ◽  
Host Diversity ◽  
Viral Loads ◽  
The United Kingdom ◽  
Low Levels

Extensive global sampling and sequencing of the pandemic virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have enabled researchers to monitor its spread and to identify concerning new variants. Two important determinants of variant spread are how frequently they arise within individuals and how likely they are to be transmitted. To characterize within-host diversity and transmission, we deep-sequenced 1313 clinical samples from the United Kingdom. SARS-CoV-2 infections are characterized by low levels of within-host diversity when viral loads are high and by a narrow bottleneck at transmission. Most variants are either lost or occasionally fixed at the point of transmission, with minimal persistence of shared diversity, patterns that are readily observable on the phylogenetic tree. Our results suggest that transmission-enhancing and/or immune-escape SARS-CoV-2 variants are likely to arise infrequently but could spread rapidly if successfully transmitted.

scholarly journals Comparison of Five Serological Assays for the Detection of SARS-CoV-2 Antibodies

Diagnostics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 78
Author(s):  
Anja Dörschug ◽  
Julian Schwanbeck ◽  
Andreas Hahn ◽  
Anke Hillebrecht ◽  
Sabine Blaschke ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Blood Donor ◽  
Immunoglobulin G ◽  
The Other ◽  
Specific Antibodies ◽  
Diagnostic Assays ◽  
Immunoglobulin Class ◽  
Corona Virus ◽  
Immunoglobulin Subclass

Serological assays can contribute to the estimation of population proportions with previous immunologically relevant contact with the Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) virus. In this study, we compared five commercially available diagnostic assays for the diagnostic identification of SARS-CoV-2-specific antibodies. Depending on the assessed immunoglobulin subclass, recorded sensitivity ranged from 17.0% to 81.9% with best results for immunoglobulin G. Specificity with blood donor sera ranged from 90.2% to 100%, with sera from EBV patients it ranged from 84.3% to 100%. Agreement from fair to nearly perfect was recorded depending on the immunoglobulin class between the assays, the with best results being found for immunoglobulin G. Only for this immunoglobulin class was the association between later sample acquisition times (about three weeks after first positive PCR results) and positive serological results in COVID-19 patients confirmed. In conclusion, acceptable and comparable reliability for the assessed immunoglobulin G-specific assays could be shown, while there is still room for improvement regarding the reliability of the assays targeting the other immunoglobulin classes.

scholarly journals Immunological imprinting of the antibody response in COVID-19 patients

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Teresa Aydillo ◽  
Alexander Rombauts ◽  
Daniel Stadlbauer ◽  
Sadaf Aslam ◽  
Gabriela Abelenda-Alonso ◽  
...  
Keyword(s):  
Immune Response ◽  
Severe Acute Respiratory Syndrome ◽  
Antibody Response ◽  
Humoral Immune Response ◽  
Nucleocapsid Protein ◽  
Spike Protein ◽  
Ongoing Research ◽  
Variable Regions ◽  
Humoral Immune ◽  
Human Coronaviruses

AbstractIn addition to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), humans are also susceptible to six other coronaviruses, for which consecutive exposures to antigenically related and divergent seasonal coronaviruses are frequent. Despite the prevalence of COVID-19 pandemic and ongoing research, the nature of the antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Here we longitudinally profile the early humoral immune response against SARS-CoV-2 in hospitalized coronavirus disease 2019 (COVID-19) patients and quantify levels of pre-existing immunity to OC43, HKU1 and 229E seasonal coronaviruses, and find a strong back-boosting effect to conserved but not variable regions of OC43 and HKU1 betacoronaviruses spike protein. However, such antibody memory boost to human coronaviruses negatively correlates with the induction of IgG and IgM against SARS-CoV-2 spike and nucleocapsid protein. Our findings thus provide evidence of immunological imprinting by previous seasonal coronavirus infections that can potentially modulate the antibody profile to SARS-CoV-2 infection.

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