High epitope density in a single protein molecule significantly enhances antigenicity as well as immunogenicity: a novel strategy for modern vaccine development and a preliminary investigation about B?cell discrimination of monomeric proteins

2005 ◽  
Vol 35 (2) ◽  
pp. 505-514 ◽  
Author(s):  
Wanli Liu ◽  
Ying-Hua Chen
Keyword(s):  
B Cell ◽  
Vaccine Development ◽  
Preliminary Investigation ◽  
Protein Molecule ◽  
Single Protein ◽  
Epitope Density ◽  
Novel Strategy ◽  
Monomeric Proteins ◽  
Cell Discrimination

scholarly journals Evolution of immune responses to SARS-CoV-2 in mild-moderate COVID-19

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Adam K. Wheatley ◽  
Jennifer A. Juno ◽  
Jing J. Wang ◽  
Kevin J. Selva ◽  
Arnold Reynaldi ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Vaccine Development ◽  
Natural Infection ◽  
Population Level ◽  
Cell Dynamics ◽  
Follicular Helper ◽  
Cell Immunity ◽  
Specific Igg ◽  
Over Time

AbstractThe durability of infection-induced SARS-CoV-2 immunity has major implications for reinfection and vaccine development. Here, we show a comprehensive profile of antibody, B cell and T cell dynamics over time in a cohort of patients who have recovered from mild-moderate COVID-19. Binding and neutralising antibody responses, together with individual serum clonotypes, decay over the first 4 months post-infection. A similar decline in Spike-specific CD4+ and circulating T follicular helper frequencies occurs. By contrast, S-specific IgG+ memory B cells consistently accumulate over time, eventually comprising a substantial fraction of circulating the memory B cell pool. Modelling of the concomitant immune kinetics predicts maintenance of serological neutralising activity above a titre of 1:40 in 50% of convalescent participants to 74 days, although there is probably additive protection from B cell and T cell immunity. This study indicates that SARS-CoV-2 immunity after infection might be transiently protective at a population level. Therefore, SARS-CoV-2 vaccines might require greater immunogenicity and durability than natural infection to drive long-term protection.

scholarly journals A Systems Biology Approach Identifies B Cell Maturation Antigen (BCMA) as a Biomarker Reflecting Oral Vaccine Induced IgA Antibody Responses in Humans

2021 ◽  
Vol 12 ◽  
Author(s):  
Lynda Mottram ◽  
Anna Lundgren ◽  
Ann-Mari Svennerholm ◽  
Susannah Leach
Keyword(s):  
Systems Biology ◽  
Immune Responses ◽  
B Cell ◽  
Vaccine Development ◽  
Oral Vaccine ◽  
Antibody Responses ◽  
Cell Maturation ◽  
Antigen Specificity ◽  
B Cell Maturation ◽  
B Cell Maturation Antigen

Vaccines against enteric diseases could improve global health. Despite this, only a few oral vaccines are currently available for human use. One way to facilitate such vaccine development could be to identify a practical and relatively low cost biomarker assay to assess oral vaccine induced primary and memory IgA immune responses in humans. Such an IgA biomarker assay could complement antigen-specific immune response measurements, enabling more oral vaccine candidates to be tested, whilst also reducing the work and costs associated with early oral vaccine development. With this in mind, we take a holistic systems biology approach to compare the transcriptional signatures of peripheral blood mononuclear cells isolated from volunteers, who following two oral priming doses with the oral cholera vaccine Dukoral®, had either strong or no vaccine specific IgA responses. Using this bioinformatical method, we identify TNFRSF17, a gene encoding the B cell maturation antigen (BCMA), as a candidate biomarker of oral vaccine induced IgA immune responses. We then assess the ability of BCMA to reflect oral vaccine induced primary and memory IgA responses using an ELISA BCMA assay on a larger number of samples collected in clinical trials with Dukoral® and the oral enterotoxigenic Escherichia coli vaccine candidate ETVAX. We find significant correlations between levels of BCMA and vaccine antigen-specific IgA in antibodies in lymphocyte secretion (ALS) specimens, as well as with proportions of circulating plasmablasts detected by flow cytometry. Importantly, our results suggest that levels of BCMA detected early after primary mucosal vaccination may be a biomarker for induction of long-lived vaccine specific memory B cell responses, which are otherwise difficult to measure in clinical vaccine trials. In addition, we find that ALS-BCMA responses in individuals vaccinated with ETVAX plus the adjuvant double mutant heat-labile toxin (dmLT) are significantly higher than in subjects given ETVAX only. We therefore propose that as ALS-BCMA responses may reflect the total vaccine induced IgA responses to oral vaccination, this BCMA ELISA assay could also be used to estimate the total adjuvant effect on vaccine induced-antibody responses, independently of antigen specificity, further supporting the usefulness of the assay.

scholarly journals Convergent antibody responses associated with broad neutralization of hepatitis C virus and clearance of infection

2021 ◽  
Author(s):  
Nicole E. Skinner ◽  
Clinton O. Ogega ◽  
Nicole Frumento ◽  
Kaitlyn E. Clark ◽  
Srinivasan Yegnasubramanian ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cell ◽  
Early Development ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
High Plasma ◽  
Spontaneous Clearance ◽  
Cell Repertoire ◽  
Molecular Features

AbstractEarly development of broadly neutralizing antibodies (bNAbs) targeting the hepatitis C virus (HCV) envelope glycoprotein E2 is associated with spontaneous clearance of infection, so induction of bNAbs is a major goal of HCV vaccine development. However, much remains to be learned at a molecular level about protective E2-reactive antibodies, since HCV infection persists in some individuals despite early development of broadly neutralizing plasma. To examine B cell repertoire features associated with broad neutralization and viral clearance, we performed RNA sequencing of the B cell receptors (BCRs) of HCV E2-reactive B cells of people with cleared or persistent HCV, including subjects with high or low plasma neutralizing breadth in both clearance and persistence groups. We identified many E2-reactive public BCR clonotypes, which are antibody clones with the same V and J-genes and identical CDR3 sequences, shared among subjects grouped by either clearance or neutralization status. The majority (89) of these public clonotypes were shared by two subjects with broad plasma neutralizing activity and cleared infection, but not found in subjects with high plasma neutralizing breadth and persistent infection. We cloned a potent, cross-reactive neutralizing monoclonal antibody (mAb) by pairing the most abundant public heavy and light chains from these two subjects, providing evidence that broadly E2-reactive public clonotypes arise in a subset of individuals with broadly neutralizing plasma and spontaneous clearance of infection. Further characterization of the molecular features and function of these antibodies can inform HCV vaccine development.

Novel strategy to treat a case of recurrent lymphocytic hypophysitis using rituximab

2012 ◽  
Vol 116 (6) ◽  
pp. 1318-1323 ◽  
Author(s):  
Matthew Schreckinger ◽  
Todd Francis ◽  
Gary Rajah ◽  
Jay Jagannathan ◽  
Murali Guthikonda ◽  
...  
Keyword(s):  
B Cell ◽  
Lymphocytic Hypophysitis ◽  
Neurological Deficits ◽  
Sellar Mass ◽  
Short Course ◽  
Autoimmune Condition ◽  
Cd20 Antibody ◽  
Novel Strategy ◽  
Anti Cd20 ◽  
The Right

Lymphocytic hypophysitis is an uncommon autoimmune condition that often results in significant morbidity. Although most cases resolve spontaneously or after a short course of steroids, rarely, refractory cases can cause persistent neurological deficits despite aggressive medical and surgical management. A 41-year-old woman presented with progressive visual loss in the left eye and was found to have a sellar mass. She underwent transsphenoidal surgery because of lesion enlargement. Histopathology was consistent with adenohypophysitis with B-cell predominance. Despite steroid treatment, her neurological condition worsened and she experienced loss of vision in the right eye. Craniotomy with decompression of the right optic nerve was performed. Her condition improved initially, but she continued to have progressive visual compromise over the following months. She was therefore treated with rituximab, a monoclonal antibody against B cells. Her vision improved significantly within a few weeks. There was no clinical or radiographic exacerbation 2 years after starting immunotherapy. Rituximab, an anti-CD20 antibody that specifically depletes B lymphocytes, can be an effective treatment strategy for patients with steroid-refractory, B cell–predominant lymphocytic hypophysitis.

scholarly journals Activated CARD11 accelerates germinal center kinetics, promoting mTORC1 and terminal differentiation

2018 ◽  
Vol 215 (9) ◽  
pp. 2445-2461 ◽  
Author(s):  
Michelle N. Wray-Dutra ◽  
Raghav Chawla ◽  
Kerri R. Thomas ◽  
Brenda J. Seymour ◽  
Tanvi Arkatkar ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Germinal Center ◽  
Terminal Differentiation ◽  
B Cell Differentiation ◽  
Activating Mutations ◽  
Class Switch ◽  
Mtorc1 Signaling ◽  
Activating Mutation ◽  
Novel Strategy

Activating mutations in the adapter protein CARD11 associated with diffuse large B cell lymphomas (DLBCLs) are predicted to arise during germinal center (GC) responses, leading to inappropriate activation of NF-κB signaling. Here, we modeled the B cell–intrinsic impact of the L251P activating mutation in CARD11 (aCARD11) on the GC response. Global B cell aCARD11 expression led to a modest increase in splenic B cells and a severe reduction in B1 B cell numbers, respectively. Following T cell–dependent immunization, aCARD11 cells exhibited increased rates of GC formation, resolution, and differentiation. Restriction of aCARD11 to GC B cells similarly altered the GC response and B cell differentiation. In this model, aCARD11 promoted dark zone skewing along with increased cycling, AID levels, and class switch recombination. Furthermore, aCard11 GC B cells displayed increased biomass and mTORC1 signaling, suggesting a novel strategy for targeting aCARD11-driven DLBCL. While aCARD11 potently impacts GC responses, the rapid GC contraction suggests it requires collaboration with events that limit terminal differentiation to promote lymphoma.

scholarly journals B-cell–lineage immunogen design in vaccine development with HIV-1 as a case study

2012 ◽  
Vol 30 (5) ◽  
pp. 423-433 ◽  
Author(s):  
Barton F Haynes ◽  
Garnett Kelsoe ◽  
Stephen C Harrison ◽  
Thomas B Kepler
Keyword(s):  
B Cell ◽  
Vaccine Development ◽  
Cell Lineage ◽  
Immunogen Design ◽  
Hiv 1

Highly immunogenic influenza virus-like particles containing B-cell-activating factor (BAFF) for multi-subtype vaccine development

2019 ◽  
Vol 164 ◽  
pp. 12-22 ◽  
Author(s):  
Jo-Yu Hong ◽  
Ting-Hsuan Chen ◽  
Yu-Jou Chen ◽  
Chia-Chyi Liu ◽  
Jia-Tsrong Jan ◽  
...  
Keyword(s):  
Influenza Virus ◽  
B Cell ◽  
Vaccine Development ◽  
Virus Like Particles ◽  
B Cell Activating Factor

scholarly journals Water-mediated influence of a crowded environment on internal vibrations of a protein molecule

2016 ◽  
Vol 18 (6) ◽  
pp. 4881-4890 ◽  
Author(s):  
Anna Kuffel ◽  
Jan Zielkiewicz
Keyword(s):  
Protein Molecule ◽  
Protein Molecules ◽  
Single Protein ◽  
Crowded Environment ◽  
Internal Vibrations

The influence of crowding on the protein inner dynamics is examined by putting a single protein molecule close to one or two neighboring protein molecules.

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