scholarly journals At the Intersection Between SARS-CoV-2, Macrophages and the Adaptive Immune Response: A Key Role for Antibody-Dependent Pathogenesis But Not Enhancement of Infection in COVID-19

2021 ◽  
Author(s):  
Jennifer K. DeMarco ◽  
Wiliam E. Severson ◽  
Daniel R. DeMarco ◽  
Gregory Pogue ◽  
Jon Gabbard ◽  
...  
Keyword(s):  
Immune Response ◽  
Neutralizing Antibodies ◽  
Distress Syndrome ◽  
Severe Disease ◽  
Adaptive Immune Response ◽  
Economic Damage ◽  
Monocyte Activation ◽  
Adaptive Immune ◽  
Respiratory Epithelia ◽  
Peripheral Monocyte

AbstractSince entering the world stage in December of 2019, SARS-CoV-2 has impacted every corner of the globe with over 1.48 million deaths and caused untold economic damage. Infections in humans range from asymptomatic to severe disease associated with dysregulation of the immune system leading to the development of acute respiratory distress syndrome (ARDs).The distinct shift in peripheral monocyte activation and infiltration of these cells into the respiratory tract in ARDs patients suggests severe COVID-19 may largely result from damage to the respiratory epithelia by improperly activated macrophages. Here, we present evidence that dysregulation of the immune response in COVID-19 begins with activation of macrophages by non-neutralizing antibodies and induction of ACE2 expression, rendering these cells susceptible to killing by SARS-CoV-2. Death of macrophages occurs independently of viral replication and leads to the release of inflammatory mediators and modulation of the susceptibility of downstream epithelial cells to SARS-CoV-2.

scholarly journals Pattern Recognition Proteins: First Line of Defense Against Coronaviruses

2021 ◽  
Vol 12 ◽  
Author(s):  
Carlos A. Labarrere ◽  
Ghassan S. Kassab
Keyword(s):  
Immune Response ◽  
Pattern Recognition ◽  
Global Economy ◽  
Rna Viruses ◽  
Severe Disease ◽  
Adaptive Immune Response ◽  
Adaptive Immune ◽  
Recognition Protein ◽  
Pattern Recognition Protein

The rapid outbreak of COVID-19 caused by the novel coronavirus SARS-CoV-2 in Wuhan, China, has become a worldwide pandemic affecting almost 204 million people and causing more than 4.3 million deaths as of August 11 2021. This pandemic has placed a substantial burden on the global healthcare system and the global economy. Availability of novel prophylactic and therapeutic approaches are crucially needed to prevent development of severe disease leading to major complications both acutely and chronically. The success in fighting this virus results from three main achievements: (a) Direct killing of the SARS-CoV-2 virus; (b) Development of a specific vaccine, and (c) Enhancement of the host’s immune system. A fundamental necessity to win the battle against the virus involves a better understanding of the host’s innate and adaptive immune response to the virus. Although the role of the adaptive immune response is directly involved in the generation of a vaccine, the role of innate immunity on RNA viruses in general, and coronaviruses in particular, is mostly unknown. In this review, we will consider the structure of RNA viruses, mainly coronaviruses, and their capacity to affect the lungs and the cardiovascular system. We will also consider the effects of the pattern recognition protein (PRP) trident composed by (a) Surfactant proteins A and D, mannose-binding lectin (MBL) and complement component 1q (C1q), (b) C-reactive protein, and (c) Innate and adaptive IgM antibodies, upon clearance of viral particles and apoptotic cells in lungs and atherosclerotic lesions. We emphasize on the role of pattern recognition protein immune therapies as a combination treatment to prevent development of severe respiratory syndrome and to reduce pulmonary and cardiovascular complications in patients with SARS-CoV-2 and summarize the need of a combined therapeutic approach that takes into account all aspects of immunity against SARS-CoV-2 virus and COVID-19 disease to allow mankind to beat this pandemic killer.

scholarly journals SARS-CoV-2 Serology Status Detected by Commercialized Platforms Distinguishes Previous Infection and Vaccination Adaptive Immune Responses

2021 ◽  
Author(s):  
Raymond T. Suhandynata ◽  
Nicholas J. Bevins ◽  
Jenny T. Tran ◽  
Deli Huang ◽  
Melissa A. Hoffman ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Natural Infection ◽  
Adaptive Immune Response ◽  
Antibody Assay ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Previous Infection ◽  
A Cell

AbstractBackgroundThe severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected over 110 million individuals and led to 2.5 million deaths worldwide. As more individuals are vaccinated, the clinical performance and utility of SARS-CoV-2 serology platforms needs to be evaluated.MethodsThe ability of four commercial SARS-CoV-2 serology platforms to detect previous infection or vaccination were evaluated using a cohort of 53 SARS-CoV-2 PCR-positive patients, 89 SARS-CoV-2-vaccinated healthcare workers (Pfizer or Moderna), and 127 SARS-CoV-2 negative patients. Serology results were compared to a cell based SARS-CoV-2 pseudovirus (PSV) neutralizing antibodies assay.ResultsThe Roche S-(spike) antibody and Diazyme neutralizing antibodies (NAbs) assays detected adaptive immune response in 100.0% and 90.1% of vaccinated individuals who received two-doses of vaccine (initial and booster), respectively. The Roche N-(nucleocapsid) antibody assay and Diazyme IgG assay did not detect adaptive immune response in vaccinated individuals. The Diazyme Nabs assay correlated with the PSV SARS-CoV-2 ID50 neutralization titers (R2= 0.70), while correlation of the Roche S-antibody assay was weaker (R2= 0.39). Median PSV SARS-CoV-2 ID50 titers more than doubled in vaccinated individuals who received two-doses of the Moderna vaccine (ID50: 597) compared to individuals that received a single dose (ID50: 284).ConclusionsThe Roche S-antibody and Diazyme NAbs assays robustly detected adaptive immune responses in SARS-CoV-2 vaccinated individuals and SARS-CoV-2 infected individuals. The Diazyme NAbs assay strongly correlates with the PSV SARS-CoV-2 NAbs in vaccinated individuals. Understanding the reactivity of commercially available serology platforms is important when distinguishing vaccination response versus natural infection.SummaryThe Roche S (spike protein)-antibody and Diazyme neutralizing-antibodies (NAbs) assays were evaluated for their clinical utility in the detection of SARS-CoV-2 related adaptive immune responses by testing SARS-CoV-2 PCR-confirmed patients, SARS-CoV-2-vaccinated individuals, and SARS-CoV-2-negative individuals. Commercial serology results were compared to results generated using a cell-based SARS-CoV-2 pseudovirus (PSV) NAbs assay and previously validated SARS-CoV-2 commercial serology assays (Roche N (nucleocapsid protein) antibody and Diazyme IgG). We demonstrate that the Roche S-antibody and Diazyme NAbs assays detected adaptive immune response in SARS-CoV-2 vaccinated individuals and the presence of SARS-CoV-2 PSV NAbs. The Roche S-antibody assay had an observed positive percent agreement (PPA) of 100% for individuals who received two doses of the Pfizer or Moderna vaccine. By contrast, the Roche N assay and Diazyme IgG assay did not detect vaccine adaptive immune responses. Our findings also indicate that the Diazyme NAbs assay correlates strongly with the levels of SARS-CoV-2 ID50 neutralization titers using the PSV Nab assay in vaccinated individuals.

scholarly journals SARS-CoV-2 and interferon blockade

2020 ◽  
Vol 26 (1) ◽  
Author(s):  
Betty Diamond ◽  
Bruce T. Volpe ◽  
Sonya VanPatten ◽  
Yousef Al Abed
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Innate Immune System ◽  
Neutralizing Antibodies ◽  
Cytotoxic T Cells ◽  
Adaptive Immune Response ◽  
Innate Immune ◽  
Interferon Production ◽  
Therapeutic Implications ◽  
Adaptive Immune

Abstract The response to viral infection generally includes an activation of the adaptive immune response to produce cytotoxic T cells and neutralizing antibodies. We propose that SARS-CoV-2 activates the innate immune system through the renin-angiotensin and kallikrein-bradykinin pathways, blocks interferon production and reduces an effective adaptive immune response. This model has therapeutic implications.

scholarly journals A Nanoscaffolded Spike-RBD Vaccine Provides Protection against SARS-CoV-2 with Minimal Anti-Scaffold Response

Vaccines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 431
Author(s):  
Duško Lainšček ◽  
Tina Fink ◽  
Vida Forstnerič ◽  
Iva Hafner-Bratkovič ◽  
Sara Orehek ◽  
...  
Keyword(s):  
Immune Response ◽  
Neutralizing Antibodies ◽  
Specific Antigen ◽  
Adaptive Immune Response ◽  
Adaptive Immune System ◽  
T Cell Response ◽  
Viral Neutralization ◽  
Adaptive Immune ◽  
Lumazine Synthase ◽  
Antibody Titers

The response of the adaptive immune system is augmented by multimeric presentation of a specific antigen, resembling viral particles. Several vaccines have been designed based on natural or designed protein scaffolds, which exhibited a potent adaptive immune response to antigens; however, antibodies are also generated against the scaffold, which may impair subsequent vaccination. In order to compare polypeptide scaffolds of different size and oligomerization state with respect to their efficiency, including anti-scaffold immunity, we compared several strategies of presentation of the RBD domain of the SARS-CoV-2 spike protein, an antigen aiming to generate neutralizing antibodies. A comparison of several genetic fusions of RBD to different nanoscaffolding domains (foldon, ferritin, lumazine synthase, and β-annulus peptide) delivered as DNA plasmids demonstrated a strongly augmented immune response, with high titers of neutralizing antibodies and a robust T-cell response in mice. Antibody titers and virus neutralization were most potently enhanced by fusion to the small β-annulus peptide scaffold, which itself triggered a minimal response in contrast to larger scaffolds. The β-annulus fused RBD protein increased residence in lymph nodes and triggered the most potent viral neutralization in immunization by a recombinant protein. Results of the study support the use of a nanoscaffolding platform using the β-annulus peptide for vaccine design.

scholarly journals Stochastic Model of the Adaptive Immune Response Predicts Disease Severity and Captures Enhanced Cross-Reactivity in Natural Dengue Infections

2021 ◽  
Vol 12 ◽  
Author(s):  
Hung D. Nguyen ◽  
Sidhartha Chaudhury ◽  
Adam T. Waickman ◽  
Heather Friberg ◽  
Jeffrey R. Currier ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Stochastic Model ◽  
Disease Severity ◽  
Secondary Infection ◽  
Severe Disease ◽  
Adaptive Immune Response ◽  
Cross Reactivity ◽  
Adaptive Immune ◽  
Severe Manifestation

The dengue virus circulates as four distinct serotypes, where a single serotype infection is typically asymptomatic and leads to acquired immunity against that serotype. However, the developed immunity to one serotype is thought to underlie the severe manifestation of the disease observed in subsequent infections from a different serotype. We developed a stochastic model of the adaptive immune response to dengue infections. We first delineated the mechanisms initiating and sustaining adaptive immune responses during primary infections. We then contrasted these immune responses during secondary infections of either a homotypic or heterotypic serotype to understand the role of pre-existing and reactivated immune pathways on disease severity. Comparison of non-symptomatic and severe cases from heterotypic infections demonstrated that overproduction of specific antibodies during primary infection induces an enhanced population of cross-reactive antibodies during secondary infection, ultimately leading to severe disease manifestations. In addition, the level of disease severity was found to correlate with immune response kinetics, which was dependent on beginning lymphocyte levels. Our results detail the contribution of specific lymphocytes and antibodies to immunity and memory recall that lead to either protective or pathological outcomes, allowing for the understanding and determination of mechanisms of protective immunity.

scholarly journals Down-regulation of SARS-CoV-2 neutralizing antibodies in vaccinated smokers

2021 ◽  
Author(s):  
Jiahui Zhang ◽  
Fei Teng ◽  
Xiaomei Zhang ◽  
Hongye Wang ◽  
Te Liang ◽  
...  
Keyword(s):  
Immune Response ◽  
Neutralizing Antibodies ◽  
Adaptive Immune Response ◽  
Vaccine Dose ◽  
Breakthrough Infection ◽  
Adaptive Immune ◽  
Smoking Group ◽  
Low Levels ◽  
Student’S T ◽  
Student’S T Test

AbstractVaccination is an effective approach to help control coronavirus disease 2019 (COVID-19). However, since the vaccines produce a heterogenous immune response, the risk of breakthrough infection is increased in vaccinated individuals who generate low levels of neutralizing antibodies (NAbs). It is therefore paramount in the fight against COVID-19 to identify individuals who have a higher risk of breakthrough infection despite being vaccinated. Here we addressed the effect of cigarette smoking on the production of neutralizing antibodies (NAbs) following COVID-19 vaccination since smoking profoundly suppresses the adaptive immune response to pathogen infection and the association between vaccination and smoking remains unclear. The SARS-CoV-2 Spike antibodies and NAbs (days 0, 14, 42, and 90) were measured in 164 participants received two vaccine doses of an inactivated vaccine (Sinovac-CoronaVac) longitudinally. Anti-Spike antibodies was elevated 14 and 42 days after COVID-19 vaccination compared to baseline (i.e., “Day 0”). Notably, RBD antibodies showed significantly higher expression in the nonsmoking group (n=153) than the smoking (n=11) group on day 42 (p<0.0001, Student’s t-test). NAbs continually increased after the first and second vaccine dose, peaking on day 42. NAbs titers then significantly decreased until day 90. Compared to nonsmokers, the NAb levels in smokers remained low throughout the period of testing. The median NAb titers in the smoking group was 1.40-, 1.32-, or 3.00-fold lower than that of nonsmoking group on day 14, 42, or 90, respectively. Altogether, our results indicate that smoking is a specific risk factor for COVID-19 breakthrough infection following vaccination.

scholarly journals Low Innate Immunity and Lagged Adaptive Immune Response in the Re-Tested Viral RNA Positivity of a COVID-19 Patient

2021 ◽  
Vol 12 ◽  
Author(s):  
Changchun Lai ◽  
Xinglong Liu ◽  
Qihong Yan ◽  
Hualiang Lv ◽  
Lei Zhou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
B Cell ◽  
Antigen Presentation ◽  
Neutralizing Antibodies ◽  
Adaptive Immune Response ◽  
Viral Rna ◽  
Lung Lesions ◽  
Adaptive Immune ◽  
Cell Counts

Recent studies have highlighted observations regarding re-tested positivity (RP) of SARS-CoV-2 RNA in discharged COVID-19 patients, however, the immune mechanisms underlying SARS-CoV-2 RNA RP in immunocompetent patients remain elusive. Herein, we describe the case of an immunocompetent COVID-19 patient with moderate symptoms who was twice re-tested as positive for SARS-CoV-2 RNA, and the period between first and third viral RNA positivity was 95 days, longer than previously reported (18–25 days). The chest computed tomography findings, plasma anti-SARS-CoV-2 antibody, neutralizing antibodies (NAbs) titer, and whole blood transcriptic characteristics in the viral RNA RP patient and other COVID-19 patients were analyzed. During the SARS-CoV-2 RNA RP period, new lung lesions were observed. The COVID-19 patient with viral RNA RP had delayed seroconversion of anti-spike/receptor-binding domain (RBD) IgA antibody and NAbs and were accompanied with disappearance of the lung lesions. Further experimental data validated that NAbs titer was significantly associated with anti-RBD IgA and IgG, and anti-spike IgG. The RP patient had lower interferon-, T cells- and B cell-related genes expression than non-RP patients with mild-to-moderate symptoms, and displayed lower cytokines and chemokines gene expression than severe patients. Interestingly, the RP patient had low expression of antigen presentation-related genes and low B cell counts which might have contributed to the delayed anti-RBD specific antibody and low CD8+ cell response. Collectively, delayed antigen presentation-related gene expression was found related to delayed adaptive immune response and contributed to the SARS-CoV-2 RNA RP in this described immunocompetent patient.

scholarly journals Broadly Neutralizing Antibodies against HIV-1 As a Novel Aspect of the Immune Response

Acta Naturae ◽  
2015 ◽  
Vol 7 (4) ◽  
pp. 11-21 ◽  
Author(s):  
D. N. Shcherbakov ◽  
A. Yu. Bakulina ◽  
L. I. Karpenko ◽  
A. A. Ilyichev
Keyword(s):  
Immune Response ◽  
Neutralizing Antibodies ◽  
Somatic Mutations ◽  
Adaptive Immune Response ◽  
Mutation Rates ◽  
Broadly Neutralizing Antibodies ◽  
Adaptive Immune ◽  
Immunodeficiency Virus ◽  
Variable Loops ◽  
Hiv 1

The human immunodeficiency virus-1 (HIV-1) has the ability to evade the adaptive immune response due to high mutation rates. Soon after the discovery of HIV-1, it was originally proposed that neutralizing of antibodies to the virus occurs rarely or cannot be elicited at all. In the 1990s, there appeared reports that sera of select HIV-1-infected individuals contained antibodies capable of neutralizing different virus subtypes. Such antibodies were named broadly neutralizing antibodies (bNAbs). Since 2009, the development of new cell technologies has intensified research efforts directed at identifying new bNAbs with a neutralization potency of over 90% of primary HIV-1 isolates. These antibodies have unique characteristics which include high levels of somatic mutations and unusually long variable loops that penetrate through the glycan shield of HIV-1 Env to contact the protein surface. In this review, we will attempt to summarize the latest data on bNAbs against HIV-1 in terms of their interactions with the sites of vulnerability on HIV-1 glycoproteins.

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