scholarly journals Durable SARS-CoV-2 B cell immunity after mild or severe disease

2020 ◽  
Author(s):  
Clinton O. Ogega ◽  
Nicole E. Skinner ◽  
Paul W. Blair ◽  
Han-Sol Park ◽  
Kirsten Littlefield ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Humoral Immunity ◽  
Neutralizing Antibodies ◽  
Severe Disease ◽  
Flow Cytometric Analysis ◽  
Neutralizing Antibody ◽  
Cell Mediated Immunity ◽  
Specific Class ◽  
Cell Immunity

AbstractMultiple studies have shown loss of SARS-CoV-2 specific antibodies over time after infection, raising concern that humoral immunity against the virus is not durable. If immunity wanes quickly, millions of people may be at risk for reinfection after recovery from COVID-19. However, memory B cells (MBC) could provide durable humoral immunity even if serum neutralizing antibody titers decline. We performed multi-dimensional flow cytometric analysis of S protein receptor binding domain (S-RBD)-specific MBC in cohorts of ambulatory COVID-19 patients with mild disease, and hospitalized patients with moderate to severe disease, at a median of 54 (39-104) days after onset of symptoms. We detected S-RBD-specific class-switched MBC in 13 out of 14 participants, including 4 of the 5 participants with lowest plasma levels of anti-S-RBD IgG and neutralizing antibodies. Resting MBC (rMBC) made up the largest proportion of S-RBD-specific class-switched MBC in both cohorts. FCRL5, a marker of functional memory when expressed on rMBC, was dramatically upregulated on S-RBD-specific rMBC. These data indicate that most SARS-CoV-2-infected individuals develop S-RBD-specific, class-switched MBC that phenotypically resemble germinal center-derived B cells induced by effective vaccination against other pathogens, providing evidence for durable B cell-mediated immunity against SARS-CoV-2 after recovery from mild or severe COVID-19 disease.Graphical Abstract

scholarly journals Humoral immunity in atherosclerosis and myocardial infarction: from B cells to antibodies

2021 ◽  
Author(s):  
Florentina Porsch ◽  
Ziad Mallat ◽  
Christoph J Binder
Keyword(s):  
Cardiovascular Disease ◽  
B Cells ◽  
B Cell ◽  
Humoral Immunity ◽  
Clinical Manifestations ◽  
Vascular Wall ◽  
Atherosclerotic Cardiovascular Disease ◽  
Cell Functions ◽  
Cell Immunity ◽  
B Cell Subsets

Abstract Immune mechanisms are critically involved in the pathogenesis of atherosclerosis and its clinical manifestations. Associations of specific antibody levels and defined B cell subsets with cardiovascular disease activity in humans as well as mounting evidence from preclinical models demonstrate a role of B cells and humoral immunity in atherosclerotic cardiovascular disease. These include all aspects of B cell immunity, the generation of antigen-specific antibodies, antigen presentation and co-stimulation of T cells, as well as production of cytokines. Through their impact on adaptive and innate immune responses and the regulation of many other immune cells, B cells mediate both protective and detrimental effects in cardiovascular disease. Several antigens derived from (oxidised) lipoproteins, the vascular wall and classical autoantigens have been identified. The unique antibody responses they trigger and their relationship with atherosclerotic cardiovascular disease are reviewed. In particular, we focus on the different effector functions of specific IgM, IgG, and IgE antibodies and the cellular responses they trigger and highlight potential strategies to target B cell functions for therapy.

scholarly journals Impaired Epstein-Barr Virus-Specific Neutralizing Antibody Response during Acute Infectious Mononucleosis Is Coincident with Global B-Cell Dysfunction

2015 ◽  
Vol 89 (17) ◽  
pp. 9137-9141 ◽  
Author(s):  
Archana Panikkar ◽  
Corey Smith ◽  
Andrew Hislop ◽  
Nick Tellam ◽  
Vijayendra Dasari ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Infectious Mononucleosis ◽  
Neutralizing Antibodies ◽  
Epstein Barr Virus ◽  
Neutralizing Antibody ◽  
Barr Virus ◽  
Cell Dysfunction ◽  
Epstein Barr ◽  
Acute Infectious Mononucleosis

Here we present evidence for previously unappreciated B-cell immune dysregulation during acute Epstein-Barr virus (EBV)-associated infectious mononucleosis (IM). Longitudinal analyses revealed that patients with acute IM have undetectable EBV-specific neutralizing antibodies and gp350-specific B-cell responses, which were associated with a significant reduction in memory B cells and no evidence of circulating antibody-secreting cells. These observations correlate with dysregulation of tumor necrosis factor family members BAFF and APRIL and increased expression of FAS on circulating B cells.

scholarly journals Characterization of neutralizing antibodies from a SARS-CoV-2 infected individual

2020 ◽  
Author(s):  
Emilie Seydoux ◽  
Leah J. Homad ◽  
Anna J. MacCamy ◽  
K. Rachael Parks ◽  
Nicholas K. Hurlburt ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Neutralizing Antibodies ◽  
Therapeutic Potential ◽  
Infected Individual ◽  
Neutralizing Antibody ◽  
Viral Envelope ◽  
List Type ◽  
Cell Lineages

ABSTRACTB cells specific for the SARS-CoV-2 S envelope glycoprotein spike were isolated from a COVID-19-infected subject using a stabilized spike-derived ectodomain (S2P) twenty-one days post-infection. Forty-four S2P-specific monoclonal antibodies were generated, three of which bound to the receptor binding domain (RBD). The antibodies were minimally mutated from germline and were derived from different B cell lineages. Only two antibodies displayed neutralizing activity against SARS-CoV-2 pseudo-virus. The most potent antibody bound the RBD in a manner that prevented binding to the ACE2 receptor, while the other bound outside the RBD. Our study indicates that the majority of antibodies against the viral envelope spike that were generated during the first weeks of COVID-19 infection are non-neutralizing and target epitopes outside the RBD. Antibodies that disrupt the SARS-CoV-2 spike-ACE2 interaction can potently neutralize the virus without undergoing extensive maturation. Such antibodies have potential preventive/therapeutic potential and can serve as templates for vaccine-design.IN BRIEFSARS-CoV-2 infection leads to expansion of diverse B cells clones against the viral spike glycoprotein (S). The antibodies bind S with high affinity despite being minimally mutated. Thus, the development of neutralizing antibody responses by vaccination will require the activation of certain naïve B cells without requiring extensive somatic mutation.HighlightsAnalysis of early B cell response to SARS-CoV-2 spike proteinMost antibodies target non-neutralizing epitopesPotent neutralizing mAb blocks the interaction of the S protein with ACE2Neutralizing antibodies are minimally mutated

scholarly journals Comparative antibody responses to the live-attenuated and recombinant herpes zoster vaccines

2021 ◽  
Author(s):  
D. Scott Schmid ◽  
Congrong Miao ◽  
Jessica Leung ◽  
Michael Johnson ◽  
Adriana Weinberg ◽  
...  
Keyword(s):  
Herpes Zoster ◽  
Advisory Committee ◽  
Humoral Immunity ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Limit Of Detection ◽  
Phase 1 ◽  
Neutralizing Antibody ◽  
The United States ◽  
Cell Mediated Immunity

Two herpes zoster (HZ) vaccines licensed in the United States are recommended by the Advisory Committee on Immunization Practices (ACIP): 1) live-attenuated vaccine (ZVL) using vOka strain varicella-zoster virus (VZV), and 2) recombinant adjuvanted vaccine (RZV) containing recombinant VZV glycoprotein E (gE). Two phase 3 clinical trials of RZV led the Advisory Committee on Immunization Practices (ACIP) to recommend it with preferred status. VZV T cell-mediated immunity (CMI), but not humoral immunity, are considered essential for protection against HZ. Published studies of humoral immunity focused on VZV-specific IgG concentration. To complement reports comparing the CMI responses to these vaccines, we compared humoral responses in ZVL and RZV recipients, emphasizing functional qualities (avidity and neutralization). Baseline avidities to a VZV glycoprotein mixture (gp) were near the upper limit of detection, but avidity to gE was much lower. Small increases in gp avidity were observed for both RZV and ZVL vaccination [19 and 12 avidity index units (AIU), respectively]. RZV boosted both gE avidity and VZV neutralizing antibody significantly more than ZVL (mean gE avidity boost: 47 AIU versus 22 AIU; mean neutralizing antibody boost: 22-fold versus 8-fold). Increases in neutralizing antibodies strongly correlated with gE avidity increases (r=0.5) and moderately with gp avidity increases (r=0.23). After 1 year, 81% of RZV recipients and only 18% of ZVL recipients retained >50% of their peak avidity boosts. These results are consistent with the CMI responses to these vaccines: RZV responses are skewed to long-term memory, whereas ZVL preferentially induces transient effector responses. IMPORTANCE These observations further distinguish the immunogenicity and duration of the immune response of the two vaccines. In addition, measurements of functional humoral immunity (IgG avidity, neutralizing antibody) in response to zoster immunization, alone or combined with other immune markers, might contribute to practical in vitro correlates of protection. Finally, combined with previous observations of the cell-mediated response to these vaccines, this study suggests that vaccine development could benefit from more expansive and granular assessments of acquired immunity during early phase 1 immunogenicity trials.

scholarly journals IL-21 is the primary common γ chain-binding cytokine required for human B-cell differentiation in vivo

Blood ◽  
2011 ◽  
Vol 118 (26) ◽  
pp. 6824-6835 ◽  
Author(s):  
Mike Recher ◽  
Lucinda J. Berglund ◽  
Danielle T. Avery ◽  
Morton J. Cowan ◽  
Andrew R. Gennery ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
B Cells ◽  
B Cell ◽  
Humoral Immunity ◽  
Antibody Responses ◽  
Cytokine Signaling ◽  
Cell Engraftment ◽  
Cell Immunity

Abstract SCID resulting from mutations in IL2RG or JAK3 is characterized by lack of T and natural killer cells; B cells are present in normal number, but antibody responses are defective. Hematopoietic cell transplantation (HCT) is curative for SCID. However, B-cell dysfunction persists in a substantial proportion of patients. We hypothesized that impaired B-cell responses after HCT in IL2RG/JAK3 deficiency results from poor donor B-cell engraftment and defective γc-dependent cytokine signaling in host B cells. To test this, and to identify which γc cytokine(s) is critical for humoral immunity, we studied 28 transplanted patients with IL2RG/JAK3 deficiency. Lack of donor B-cell engraftment associated with persistent humoral dysfunction and significantly reduced memory B cells. B-cell proliferation induced by CD40L alone or together with CpG, anti-Ig, IL-4, IL-10, or IL-13 was comparable in healthy controls and in post-HCT SCID patients, irrespective of their chimerism status. However, in vitro stimulation with CD40L/IL-21 induced B-cell proliferation, plasmablast differentiation, and antibody secretion in patients with donor B cells, but not in patients with autologous B cells. These data imply that IL-21–mediated signaling is critical for long-lived humoral immunity and to restore antibody responses in IL2RG/JAK3-deficient patients after HCT. Furthermore, in vitro stimulation with CD40L/IL-21 can predict in vivo B-cell immunity in IL2RG/JAK3 SCID after transplantation.

scholarly journals Seroconversion following COVID-19 vaccination: Can we optimize protective response in CD20-treated individuals?

2021 ◽  
Author(s):  
David Baker ◽  
Amy MacDougall ◽  
Angray S Kang ◽  
Klaus Schmierer ◽  
Gavin Giovannoni ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Severe Disease ◽  
Neutralizing Antibody ◽  
Vaccine Responses ◽  
Increased Risk ◽  
Cell Monitoring ◽  
Treatment Onset ◽  
Anti Cd20 ◽  
Dosing Intervals

Abstract Although there is an ever-increasing number of disease-modifying treatments for relapsing multiple sclerosis (MS), few appear to influence COVID-19 severity. There is concern about the use of anti-CD20-depleting monoclonal antibodies, due to the apparent increased risk of severe disease following SARS-CoV-2 infection and inhibition of protective anti-COVID-19 vaccine responses. These antibodies are given as maintenance infusions/injections and cause persistent depletion of CD20+ B cells, notably memory B cell populations that may be instrumental in the control of relapsing MS. However, they also continuously deplete immature and mature/naïve B cells that form the precursors for infection-protective antibody responses, thus blunting vaccine responses. Seroconversion and maintained SARS-CoV-2 neutralizing antibody levels provide protection from COVID-19. However, it is evident that poor-seroconversion occurs in the majority of individuals following initial and booster COVID-19 vaccinations, based on standard 6-monthly dosing intervals. Seroconversion may be optimized in the anti-CD20-treated population by vaccinating prior to treatment-onset or using extended/delayed interval dosing (3-6 month extension to dosing interval) in those established on therapy, with B cell monitoring until (1-3%) B cell repopulation occurs prior to vaccination. Some people will take more than a year to replete and therefore protection may depend on either the vaccine-induced T cell responses that typically occur or may require prophylactic, or rapid post-infection therapeutic, antibody or small molecule anti-viral treatment to optimise protection against COVID-19. Further studies are warranted to demonstrate the safety and efficacy of such approaches and whether or not immunity wanes prematurely as has been observed in the other populations.

scholarly journals Longitudinal characterization of humoral and cellular immunity in hospitalized COVID-19 patients reveal immune persistence up to 9 months after infection

2021 ◽  
Author(s):  
John Tyler Sandberg ◽  
Renata Varnaitė ◽  
Wanda Christ ◽  
Puran Chen ◽  
Jagadeeswara R. Muvva ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cellular Immunity ◽  
Symptom Onset ◽  
Neutralizing Antibodies ◽  
Severe Disease ◽  
Neutralizing Antibody ◽  
Immune Memory ◽  
Humoral And Cellular Immunity ◽  
Cell Responses

AbstractBackgroundInsights into early, specific humoral and cellular responses to infection with SARS-CoV-2, as well as the persistence and magnitude of resulting immune memory is important amidst the ongoing pandemic. The combination of humoral and cellular immunity will most likely contribute to protection from reinfection or severe disease.MethodsHere, we conducted a longitudinal study on hospitalized moderate and severe COVID-19 patients from the acute phase of disease into convalescence at five- and nine-months post symptom onset. Utilizing flow cytometry, serological assays as well as B cell and T cell FluoroSpot assays, we assessed the magnitude and specificity of humoral and cellular immune memory during and after human SARS-CoV-2 infection.FindingsDuring acute COVID-19, we observed an increase in germinal center activity, a substantial expansion of antibodysecreting cells, and the generation of SARS-CoV-2-neutralizing antibodies. Despite gradually decreasing antibody levels, we show persistent, neutralizing antibody titers as well as robust specific memory B cell responses and polyfunctional T cell responses at five- and nine-months after symptom onset in both moderate and severe COVID-19 patients. Long-term SARS-CoV-2 specific responses were marked by preferential targeting of spike over nucleocapsid protein.ConclusionsOur findings describe the initiation and, importantly, persistence of cellular and humoral SARS-CoV-2 specific immunological memory in hospitalized COVID-19 patients long after recovery, likely contributing towards protection against reinfection.

scholarly journals TFH Cells Induced by Vaccination and Following SIV Challenge Support Env-Specific Humoral Immunity in the Rectal-Genital Tract and Circulation of Female Rhesus Macaques

2021 ◽  
Vol 11 ◽  
Author(s):  
Sabrina Helmold Hait ◽  
Christopher James Hogge ◽  
Mohammad Arif Rahman ◽  
Ruth Hunegnaw ◽  
Zuena Mushtaq ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Humoral Immunity ◽  
Neutralizing Antibodies ◽  
Rhesus Macaques ◽  
Affinity Maturation ◽  
Cell Maturation ◽  
Female Rhesus ◽  
Specific Igg ◽  
Female Rhesus Macaques

T follicular helper (TFH) cells are pivotal in lymph node (LN) germinal center (GC) B cell affinity maturation. Circulating CXCR5+ CD4+ T (cTFH) cells have supported memory B cell activation and broadly neutralizing antibodies in HIV controllers. We investigated the contribution of LN SIV-specific TFH and cTFH cells to Env-specific humoral immunity in female rhesus macaques following a mucosal Ad5hr-SIV recombinant priming and SIV gp120 intramuscular boosting vaccine regimen and following SIV vaginal challenge. TFH and B cells were characterized by flow cytometry. B cell help was evaluated in TFH-B cell co-cultures and by real-time PCR. Vaccination induced Env-specific TFH and Env-specific memory (ESM) B cells in LNs. LN Env-specific TFH cells post-priming and GC ESM B cells post-boosting correlated with rectal Env-specific IgA titers, and GC B cells at the same timepoints correlated with vaginal Env-specific IgG titers. Vaccination expanded cTFH cell responses, including CD25+ Env-specific cTFH cells that correlated negatively with vaginal Env-specific IgG titers but positively with rectal Env-specific IgA titers. Although cTFH cells post-2nd boost positively correlated with viral-loads following SIV challenge, cTFH cells of SIV-infected and protected macaques supported maturation of circulating B cells into plasma cells and IgA release in co-culture. Additionally, cTFH cells of naïve macaques promoted upregulation of genes associated with B cell proliferation, BCR engagement, plasma cell maturation, and antibody production, highlighting the role of cTFH cells in blood B cell maturation. Vaccine-induced LN TFH and GC B cells supported anti-viral mucosal immunity while cTFH cells provided B cell help in the periphery during immunization and after SIV challenge. Induction of TFH responses in blood and secondary lymphoid organs is likely desirable for protective efficacy of HIV vaccines.

scholarly journals Homologous and Variant-Specific Memory B-Cell and Antibody Responses after SARS-CoV-2 mRNA Vaccination

2021 ◽  
Author(s):  
Iana H. Haralambieva ◽  
Jonathon M. Monroe ◽  
Diane E. Grill ◽  
Inna G Ovsyannikova ◽  
Gregory A. Poland ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Humoral Immunity ◽  
Vaccine Dose ◽  
Neutralizing Antibody ◽  
Memory B Cells ◽  
Immune Memory ◽  
Antibody Activity ◽  
Convenience Sample ◽  
Memory B Cell

Abstract. Importance. A better understanding of the immune memory and functional humoral immunity directed at the emerging Variants of Concern (VoC) strains after SARS-CoV-2 vaccination is essential for predicting the longevity of heterotypic protection. Objective. The aim of our study was to characterize functional humoral immunity (including memory B cell response) after COVID-19 mRNA vaccination and to determine/compare the reactivity of COVID-19 vaccine-induced memory B cells to the emerging SARS-CoV-2 Variants of Concern (VoC). Design, setting, participants and interventions. We designed an exploratory longitudinal observational (convenience sample-based) study at Mayo Clinic, Rochester, MN that enrolled and followed naive subjects and recovered COVID-19 subjects from Olmsted County, MN and surrounding areas after COVID-19 vaccination in January-June 2021. The study enrolled 17 relatively healthy subjects, 59% females and 94% White/Non-Hispanic or Latino with median age at enrollment 41 years. The subjects received either the BNT162b2 (Pfizer/BioNtech) or mRNA-1273 (Moderna) vaccine (n=3) and provided a blood sample at baseline, at;3 weeks after their first vaccine dose/before the second dose, and at;2 weeks after the receipt of their second vaccine dose. Main outcomes and measures. Spike-specific humoral and memory B cells responses were assessed over time after vaccination against the original Wuhan-Hu-1/vaccine and against emerging VoC strains/antigens. Results. We observed a robust neutralizing antibody response after COVID-19 mRNA vaccination, but a reduction in the functional antibody activity to several of the emerging SARS-CoV-2 VoC. Consistent with this, we also found differences in the number of isotype-switched/IgG+ MBCs responding to homologous and variant receptor-binding domain/RBDs after vaccination. We found a reduction of MBCs reactive to RBDs of Beta, Gamma and Delta SARS-CoV-2 VoC strains. Conclusion and relevance. In this exploratory study in subjects following receipt of COVID-19 mRNA vaccine, we found differences in antibody titers observed for VoCs after vaccination that are accompanied with, and can partially be explained by, decreased MBC reactivity against the VoCs. This can further attenuate the generated recall humoral immune response upon exposure to these variants.

scholarly journals Methamphetamine Compromises the Adaptive B Cell-Mediated Immunity to Antigenic Challenge in C57BL/6 Mice

2021 ◽  
Vol 3 ◽  
Author(s):  
Anum N. Mitha ◽  
Daniela Chow ◽  
Valerie Vaval ◽  
Paulina Guerrero ◽  
Dormarie E. Rivera-Rodriguez ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Adaptive Immunity ◽  
Humoral Immunity ◽  
Cell Mediated Immunity ◽  
Limited Information ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
The Impact

Methamphetamine (METH) is a substance of abuse that causes dysregulation of the innate and adaptive immunity in users. B cells are involved in the humoral component of the adaptive immunity by producing and secreting antibodies (Abs). METH modifies Ab production, although limited information on the impact of this psychostimulant on antigen (Ag)-specific humoral immune responses is available. Since T cell-dependent and T cell-independent Ags are involved in the activation of B lymphocytes, we explored the role of METH on humoral immunity to ovalbumin (OVA; T cell-dependent) and bacterial lipopolysaccharide (LPS; T cell-independent) in C57BL/6 mice. We demonstrated that METH extends the infiltration of B cells into pulmonary and splenic tissues 7 days post-Ag challenge. METH impairs Ab responses in the blood of animals challenged with OVA and LPS. Furthermore, METH diminishes the expression and distribution of IgM on B cell surface, suggesting a possible detrimental impact on users' humoral immunity to infection or autoimmunity.

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