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 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 Clearance of low levels of HCV viremia in the absence of a strong adaptive immune response

2007 ◽  
Vol 4 (1) ◽  
pp. 58 ◽  
Author(s):  
Manuela F Meyer ◽  
Marc Lehmann ◽  
Markus Cornberg ◽  
Johannes Wiegand ◽  
Michael P Manns ◽  
...  
Keyword(s):  
Immune Response ◽  
Adaptive Immune Response ◽  
Adaptive Immune ◽  
Low Levels

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 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.

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 First dose mRNA vaccination is sufficient to reactivate immunological memory to SARS-CoV-2 in ex COVID-19 subjects

2021 ◽  
Author(s):  
Alessio Mazzoni ◽  
Nicoletta Di Lauria ◽  
Laura Maggi ◽  
Lorenzo Salvati ◽  
Anna Vanni ◽  
...  
Keyword(s):  
Immune Response ◽  
Neutralizing Antibodies ◽  
Herd Immunity ◽  
Previous History ◽  
Adaptive Immune Response ◽  
Vaccine Dose ◽  
Vaccination Schedule ◽  
Humoral Immune ◽  
Future Clinical Practice ◽  
History Of

AbstractCharacterizing the adaptive immune response to COVID-19 vaccination in individuals who recovered from SARS-CoV-2 infection may define current and future clinical practice. To determine the effect of two doses BNT162b2 mRNA COVID-19 vaccination schedule in individuals who recovered from COVID-19 (ex COVID-19) compared to naïve subjects we evaluated SARS-CoV-2 spike-specific T and B cell responses, as well as specific IgG, IgM and neutralizing antibodies titres in 22 individuals who received BNT162b2 mRNA COVID-19 vaccine, 11 of which had a previous history of SARS-CoV-2 infection. Evaluations were performed before vaccination and then weekly until 7 days post second injection. Data obtained clearly showed that one vaccine dose is sufficient to increase both cellular and humoral immune response in ex COVID-19 subjects without any additional improvement after the second dose. On the contrary, the second dose is mandatory in naïve ones to further enhance the response. These results question whether a second vaccine jab in ex COVID-19 subjects is required and indicate that millions of vaccine doses may be redirected to naïve individuals, thus shortening the time to reach herd immunity.

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