scholarly journals Distinct functions of monoclonal IgG antibody depend on antigen-site specificities.

1979 ◽  
Vol 149 (4) ◽  
pp. 923-937 ◽  
Author(s):  
W Schalch ◽  
J K Wright ◽  
L S Rodkey ◽  
D G Braun
Keyword(s):  
Specific Antibody ◽  
Mechanistic Model ◽  
Single Band ◽  
Antigenic Determinants ◽  
Igg Antibody ◽  
High Affinity ◽  
Functional Differences ◽  
Group A ◽  
Antigen Site ◽  
Antibody Levels

Intraveneous hyperimmunization of selectivity bred rabbits with streptococcal group A-variant vaccines elicits antibody responses of restricted heterogeneity at high antibody levels. All antisera contain two functionally distinct antibody populations, which can be isolated in single-band purity upon analytical isoelectric focusing. Typical examples of these two kinds of single-band antibodies were investigated in great detail for several parameters by a variety of methods. 85--99% of the streptococcal group A-variant polysaccharide (Av-CHO)-specific antibody in the antisera does not precipitate the isolated 5,000 daltons poly-L-rhamnose antigen, neither agglutinates nor lyses in the presence of complement Av-CHO-coated sheep erythrocytes (SRBC), binds the radio-labeled Av-CHO with an association constant in the ragne of 10(5)--10(6) M-1, and is of terminal specificity (nonreducing end) for the linear Av-CHO. In contrast, the minor fraction of Av-CHO-specific antibody (1--15%) does precipitate the linear Av-CHO, both agglutinates and lyses Av-CHO-coated SRBC in the presence of complement, has an affinity range of 10(8)--10(9) M-1, and is of internal specificity for the Av-CHO. The antigenic determinants of the Av-CHO for the antibodies are nonoverlapping, only one Fab of the low affinity antibody can be bound whereas four Fab of the high affinity antibody are accommodated. Hence, the determinant specificity explains the functional differences observed, for there is no indication of subclass differences. A mechanistic model of the A-variant carbohydrate presentation on the vaccine appears to account best for the unbalanced levels of low and high affinity antibody.

scholarly journals Potentiating Antigen-Specific Antibody Production with Peptides Obtained from In Silico Screening for High-Affinity against MHC-II

Molecules ◽  
2019 ◽  
Vol 24 (16) ◽  
pp. 2949
Author(s):  
Yoshiro Hanyu ◽  
Yuto Komeiji ◽  
Mieko Kato
Keyword(s):  
Monoclonal Antibodies ◽  
Binding Affinity ◽  
Antibody Production ◽  
Specific Antibody ◽  
In Silico ◽  
Igg Antibody ◽  
Mhc Ii ◽  
High Affinity ◽  
Specific Antibody Production

Monoclonal antibodies with high affinity and specificity are essential for research and clinical purposes, yet remain difficult to produce. Agretope peptides that can potentiate antigen-specific antibody production have been reported recently. Here, we screened in silico for peptides with higher affinity against the agretope binding pocket in the MHC-II. The screening was based on the 3D crystal structure of a complex between MHC-II and a 14-mer peptide consisting of ovalbumin residues 323–339. Using this 14-mer peptide as template, we constructed a library of candidate peptides and screened for those that bound tightly to MHC-II. Peptide sequences that exhibited a higher binding affinity than the original ovalbumin peptide were identified. The peptide with the highest binding affinity was synthesized and its ability to boost antigen-specific antibody production in vivo and in vitro was assessed. In both cases, antigen-specific IgG antibody production was potentiated. Monoclonal antibodies were established by in vitro immunization using this peptide as immunostimulant, confirming the usefulness of such screened peptides for monoclonal antibody production.

scholarly journals Immunity after COVID-19 and vaccination: follow-up study over 1 year among medical personnel

Infection ◽  
2021 ◽  
Author(s):  
Vivian Glück ◽  
Sonja Grobecker ◽  
Josef Köstler ◽  
Leonid Tydykov ◽  
Manuela Bertok ◽  
...  
Keyword(s):  
Specific Antibody ◽  
Booster Vaccination ◽  
Medical Personnel ◽  
Dose Schedule ◽  
Igg Antibody ◽  
Cell Counts ◽  
Specific Memory ◽  
Iga Antibodies ◽  
History Of ◽  
Antibody Levels

Abstract Background The long-term course of immunity among individuals with a history of COVID-19, in particular among those who received a booster vaccination, has not been well defined so far. Methods SARS-CoV-2-specific antibody levels were measured by ELISA over 1 year among 136 health care workers infected during the first COVID-19 wave and in a subgroup after booster vaccination approximately 1 year later. Furthermore, spike-protein-reactive memory T cells were quantified approximately 7 months after the infection and after booster vaccination. Thirty healthy individuals without history of COVID-19 who were routinely vaccinated served as controls. Results Levels of SARS-CoV-2-specific IgM- and IgA-antibodies showed a rapid decay over time, whereas IgG-antibody levels decreased more slowly. Among individuals with history of COVID-19, booster vaccination induced very high IgG- and to a lesser degree IgA-antibodies. Antibody levels were significantly higher after booster vaccination than after recovery from COVID-19. After vaccination with a two-dose schedule, healthy control subjects developed similar antibody levels as compared to individuals with history of COVID-19 and booster vaccination. SARS-CoV-2-specific memory T cell counts did not correlate with antibody levels. None of the study participants suffered from a reinfection. Conclusions Booster vaccination induces high antibody levels in individuals with a history of COVID-19 that exceeds by far levels observed after recovery. SARS-CoV-2-specific antibody levels of similar magnitude were achieved in healthy, COVID-19-naïve individuals after routine two-dose vaccination.

scholarly journals Pre-Existing Humoral Immunological Memory Is Retained in Patients with Multiple Sclerosis Receiving Cladribine Therapy

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1584
Author(s):  
Tobias Moser ◽  
Ciara O’Sullivan ◽  
Christian Puttinger ◽  
Julia Feige ◽  
Georg Pilz ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Hepatitis B ◽  
Specific Antibody ◽  
Igg Antibody ◽  
Blood Concentrations ◽  
Varicella Zoster ◽  
Serum Igg ◽  
Antibody Titers ◽  
Antibody Levels ◽  
The Impact

Cladribine (CLAD) is a lymphodepleting agent approved for active relapsing multiple sclerosis (MS). The impact of CLAD on the adaptive humoral immune system has not sufficiently been studied. This study aimed to assess the influence of CLAD treatment on specific antibody titers to common pathogens. We included 18 MS patients treated with CLAD. Serum IgG antibody levels to measles, mumps, rubella, hepatitis B and varicella zoster virus (VZV), as well as diphtheria and tetanus toxins, were measured prior to the initiation of treatment and at 12 and 24 months after first CLAD administration. Moreover, specimens were longitudinally analyzed regarding absolute blood concentrations of IgG and main lymphocyte subsets. No reduction in antibody levels against measles, mumps, rubella, VZV, hepatitis B, diphtheria toxin and tetanus toxin associated with CLAD treatment was observed. Loss of seroprotection occurred in < 1%. We found no significant impact of CLAD on absolute serum IgG levels. Absolute lymphocyte counts were significantly reduced at the end of each treatment year (p < 0.00001 and p < 0.000001). This study suggests that CLAD does not interfere with the pre-existing humoral immunologic memory in terms of pathogen-specific antibody titers.

scholarly journals Pattern-Recognition Receptor Agonist-Containing Immunopotentiator CVC1302 Boosts High-Affinity Long-Lasting Humoral Immunity

2021 ◽  
Vol 12 ◽  
Author(s):  
Luping Du ◽  
Liting Hou ◽  
Xiaoming Yu ◽  
Haiwei Cheng ◽  
Jin Chen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Pattern Recognition ◽  
Humoral Immunity ◽  
Specific Antibody ◽  
Plasma Cells ◽  
Pattern Recognition Receptor ◽  
High Affinity ◽  
Mouth Disease Virus ◽  
Antibody Levels ◽  
Recognition Receptor

Ideally, a vaccine should provide life-long protection following a single administered dose. In our previous study, the immunopotentiator CVC1302, which contains pattern- recognition receptor (PRR) agonists, was demonstrated to prolong the lifetime of the humoral immune response induced by killed foot-and-mouth disease virus (FMDV) vaccine. To elucidate the mechanism by which CVC1302 induces long-term humoral immunity, we used 4-hydroxy-3-nitrophenylacetyl (NP)-OVA as a pattern antigen and administered it to mice along with CVC1302, emulsified together with Marcol 52 mineral oil (NP-CVC1302). From the results of NP-specific antibody levels, we found that CVC1302 could induce not only higher levels of NP-specific antibodies but also high-affinity NP-specific antibody levels. To detect the resulting NP-specific immune cells, samples were taken from the injection sites, draining lymph nodes (LNs), and bone marrow of mice injected with NP-CVC1302. The results of these experiments show that, compared with mice injected with NP alone, those injected with NP-CVC1302 had higher percentages of NP+ antigen-presenting cells (APCs) at the injection sites and draining LNs, higher percentages of follicular helper T cells (TFH), germinal center (GC) B cells, and NP+ plasma-blasts in the draining LNs, as well as higher percentages of NP+ long-lived plasma cells (LLPCs) in the bone marrow. Additionally, we observed that the inclusion of CVC1302 in the immunization prolonged the lifetime of LLPCs in the bone marrow by improving the transcription expression of anti-apoptotic transcription factors such as Mcl-1, Bcl-2, BAFF, BCMA, Bax, and IRF-4. This research provides a blueprint for designing new generations of immunopotentiators.

scholarly journals Structural Insight into CVB3-VLP Non-Adjuvanted Vaccine

2020 ◽  
Vol 8 (9) ◽  
pp. 1287
Author(s):  
Minna M. Hankaniemi ◽  
Mo A. Baikoghli ◽  
Virginia M. Stone ◽  
Li Xing ◽  
Outi Väätäinen ◽  
...  
Keyword(s):  
Exchange Chromatography ◽  
Scale Production ◽  
Igg Antibody ◽  
Purification Method ◽  
Microscopy Imaging ◽  
Single Particle Reconstruction ◽  
Enhanced Production ◽  
Chronic Myocarditis ◽  
Flow Filtration ◽  
Antibody Levels

Coxsackievirus B (CVB) enteroviruses are common pathogens that can cause acute and chronic myocarditis, dilated cardiomyopathy, aseptic meningitis, and they are hypothesized to be a causal factor in type 1 diabetes. The licensed enterovirus vaccines and those currently in clinical development are traditional inactivated or live attenuated vaccines. Even though these vaccines work well in the prevention of enterovirus diseases, new vaccine technologies, like virus-like particles (VLPs), can offer important advantages in the manufacturing and epitope engineering. We have previously produced VLPs for CVB3 and CVB1 in insect cells. Here, we describe the production of CVB3-VLPs with enhanced production yield and purity using an improved purification method consisting of tangential flow filtration and ion exchange chromatography, which is compatible with industrial scale production. We also resolved the CVB3-VLP structure by Cryo-Electron Microscopy imaging and single particle reconstruction. The VLP diameter is 30.9 nm on average, and it is similar to Coxsackievirus A VLPs and the expanded enterovirus cell-entry intermediate (the 135s particle), which is ~2 nm larger than the mature virion. High neutralizing and total IgG antibody levels, the latter being a predominantly Th2 type (IgG1) phenotype, were detected in C57BL/6J mice immunized with non-adjuvanted CVB3-VLP vaccine. The structural and immunogenic data presented here indicate the potential of this improved methodology to produce highly immunogenic enterovirus VLP-vaccines in the future.

Immunochemical Studies on Antithrombin III

1979 ◽  
Author(s):  
E.J. McKay
Keyword(s):  
Antithrombin Iii ◽  
The Other ◽  
Antigenic Determinants ◽  
Immunochemical Analysis ◽  
Paradoxical Effect ◽  
Test Protocol ◽  
Agar Gel ◽  
High Affinity ◽  
Time Required ◽  
Antigen Antibody

Depressed Antithrombin III (AT) levels Increase thrombic tendency in man, therefore value in assaying this protein has been established. Immunochemical analysis of AT in clinical disease has however proved controversial, consequently systematic studies were undertaken to rationalize the requirements necessary to optimise these methods in particular electro-Immunoassay. The known binding affinity of AT for heparin has been exploited to differentiate high affinity AT from its inhibitor - protease complexes and has resulted in reports stating that heparin added to the agar gel prior to electrophoresis significantly reduces the time required for completion of antigen/antibody complexes. Our studies however have demonstrated that the antibody required for quantitative analysis must be capable of not only reacting with “native” antigenic determinants of AT but also with “neo” antigens that are exposed when inhibitor-protease complexes are formed. Heparin should not be used in the test protocol, for it has a paradoxical effect on Immunopreclpltation in gels, masking some antigenic determinants of unbound - high affinity AT on one hand, and appear to disrupt the Immunoprecipitin “rocket” formed with the inhibitor-protease complexes during electrophoresis on the other.

Immunopathological mechanisms in bacterial-host interactions

1983 ◽  
Vol 303 (1114) ◽  
pp. 177-187 ◽  
Keyword(s):  
Rheumatic Fever ◽  
Group A Streptococcus ◽  
Biological Properties ◽  
Antigenic Determinants ◽  
Bacterial Host ◽  
Poststreptococcal Glomerulonephritis ◽  
Host Interactions ◽  
Disease States ◽  
Group A ◽  
Specific Tissue

The ability of bacteria to cause immunopathological damage in the host may take a variety of forms. These pathways may be conveniently grouped under three major headings: (1) organisms that can cause damage via shared antigenic determinants between host and bacterium; (2) those organisms that suppress the host’s response; and (3) organisms that release substances with specific biological properties or have receptors for specific tissue sites. The group A streptococcus is among the most versatile of these bacteria because it appears that it may use all three pathways in various streptococcal-related disease states. In rheumatic fever and chorea it appears that cross-reactive antigens play a major role in inducing immunopathological damage in that there is both a heightened humoral and cellular reaction by the host to these cross-reactive determinants. Recent evidence also indicates that rheumatic fever individuals express certain B cell antigens that may be associated with susceptibility to the disease. In the other complications of streptococcal infections, namely poststreptococcal glomerulonephritis, the bacterium uses both suppression of the host’s immune response and the excretion of a particular protein common to all nephritis-associated strains to achieve its immunopathological damage. In this context, other examples of bacterial-host interactions will be discussed as evidence for the common pathways used by microbes to cause immunopathological damage in the host.

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