scholarly journals A Note on the Potential BCG Vaccination – COVID-19 Molecular Link

Coronaviruses ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 4-6 ◽  
Author(s):  
Alex Y. Strongin ◽  
Alex Sloutsky ◽  
Piotr Cieplak
Keyword(s):  
B Cells ◽  
Mycobacterium Bovis ◽  
Sequence Homology ◽  
Experimental Studies ◽  
Memory B Cells ◽  
Bacillus Calmette Guerin ◽  
Bcg Vaccination ◽  
The Past ◽  
Specific Memory

Objective: Our goal was to elucidate a potential molecular link between the past and current tuberculosis vaccine Bacillus Calmette-Guérin (BCG; a live attenuated strain of Mycobacterium bovis) immunization policies and COVID-19. Methods: Our sequence homology analyses have demonstrated that there is an intriguing level of sequence homology between a few of the BCG and Sars-CoV-2 proteins. Results: The data suggest that the BCG-specific memory B-cells that are preserved in BCG-vaccinated patients cross-recognize SARS-CoV-2 and that this cross-recognition may affect the virus proliferation and COVID-19 severity. Conclusion: Our results can stimulate the sharply focused follow-up experimental studies.

Factor VIII-Specific Memory B-Cells in Patients with Hemophilia A.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1020-1020 ◽  
Author(s):  
Pauline M.W. van Helden ◽  
Paul H.P. Kaijen ◽  
H. Marijke van den Berg ◽  
Jan Voorberg
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Hemophilia A ◽  
Low Frequency ◽  
Memory B Cells ◽  
The Past ◽  
Specific Memory ◽  
Specific Igg ◽  
Inhibitory Antibodies

Abstract The quick anamnestic antibody response seen after recurrent exposure to antigen involves memory B- cells that, helped by T-cells, undergo rigid proliferation and subsequent differentiation into antibody producing cells. The presence of a pool of memory B-cells allows for a rapid response to antigens which quickly eliminates incoming pathogens. In the context of immune responses to therapeutic agents such as blood coagulation factor VIII (FVIII), antigenic re-stimulation of specific memory B-cells is undesirable. In approximately 25% of hemophilia A patients replacement therapy is hampered by inhibitory antibodies that bind to FVIII. Currently, the FVIII-specific memory B-cell compartment in patients with hemophilia A has remained poorly characterized. We have developed a protocol that allows for identification and quantification of circulating memory B-cells in patients with hemophilia A. CD19+ B-cells were sorted on a layer of irradiated EL4B5 thymoma cells expressing CD40L in the presence of the supernatant of mitogen-stimulated T-cells. These experimental conditions, that mimic the interaction of B-cells with an activating helper CD4+ T-cell, induce proliferation of memory B-cells and allow them to differentiate into antibody secreting cells (ASC) in an antigen-independent manner. After 9–10 days of culture, total IgG and FVIII-specific IgG was determined by ELISA and number of ASC was determined by ELISpot. We analyzed blood samples of five multi-transfused patients (>50 FVIII administrations) who never experienced any inhibitor episode, five patients who experienced inhibitory antibodies in the past but were successfully treated with immune tolerance induction and 6 patients with an inhibitor at the time of blood sampling. The ELISA set-up appeared to be more sensitive than ELISpot showing ASC producing anti-FVIII antibodies varying from 0.2–50 ng/ml. In contrast, ELISpot analysis only allowed for detection of B-cell clones producing over ~4 ng/ml of FVIII-specific IgG. Frequencies of FVIII-specific memory B-cells varied from 0–0.027% of total number of circulating peripheral B-cells. The relative amount of circulating memory B-cells did not correspond to inhibitor titers as measured in a Bethesda assay. The highest frequencies were observed in patients suffering from anamnestic response to FVIII suggesting the importance of antigenic stimulation for maintenance of memory B-cell levels. This is further supported by the low frequency that was observed in a high-titer inhibitor patient who had not been treated with FVIII for several months prior to blood sampling. Surprisingly, we detected FVIII-specific memory B-cells in two multi-transfused patients who did not experience any inhibitor episode in the past. These B-cells were present in a low frequency however and developed into ASC producing only limited amounts of anti-FVIII antibodies. These observations suggest that peripheral blood memory B-cells can develop in the absence of clinically relevant inhibitors.

scholarly journals Epidemiology of childhood tuberculosis after ceasing universal Bacillus Calmette–Guérin vaccination

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sayori Kobayashi ◽  
Takashi Yoshiyama ◽  
Kazuhiro Uchimura ◽  
Yuko Hamaguchi ◽  
Seiya Kato
Keyword(s):  
Policy Change ◽  
Vaccine Coverage ◽  
Lessons Learned ◽  
Public Health Authority ◽  
Bacillus Calmette Guerin ◽  
Notification Rate ◽  
Bcg Vaccination ◽  
The Past ◽  
Childhood Tb ◽  
Selective Vaccination

AbstractUniversal Bacillus Calmette–Guérin (BCG) vaccination is recommended in countries with high tuberculosis (TB) burden. Nevertheless, several countries have ceased universal BCG vaccination over the past 40 years, with scarce comparative epidemiological analyses regarding childhood TB after the policy change. We analysed data on childhood TB in countries that ceased universal BCG vaccination. Data sources included national/international databases, published papers, annual TB reports, and public health authority websites. Childhood TB notification rate increased in one of seven countries with available data. Pulmonary TB and TB lymphadenitis were the main causes of increasing childhood cases, while changes in severe forms of TB cases were minor. Maintaining high vaccine coverage for the target group was a common challenge after shifting selective vaccination. In some countries showing no increase in childhood TB after a BCG policy change, the majority of childhood TB cases were patients from abroad or those with overseas parents; these countries had changed immigration policies during the same period. Heterogeneity in childhood TB epidemiology was observed after ceasing universal BCG vaccination; several factors might obscure the influence of vaccination policy change. Lessons learned from these countries may aid in the development of better BCG vaccination strategies.

An optimized assay for the enumeration of antigen-specific memory B cells in different compartments of the human body

2010 ◽  
Vol 358 (1-2) ◽  
pp. 56-65 ◽  
Author(s):  
Yanran Cao ◽  
Maja Gordic ◽  
Sebastian Kobold ◽  
Nesrine Lajmi ◽  
Sabrina Meyer ◽  
...  
Keyword(s):  
B Cells ◽  
Human Body ◽  
Memory B Cells ◽  
Specific Memory

scholarly journals Induction of long-lived germinal centers associated with persisting antigen after viral infection.

1996 ◽  
Vol 183 (5) ◽  
pp. 2259-2269 ◽  
Author(s):  
M F Bachmann ◽  
B Odermatt ◽  
H Hengartner ◽  
R M Zinkernagel
Keyword(s):  
T Cell ◽  
B Cells ◽  
Viral Infection ◽  
Neutralizing Antibody ◽  
Germinal Centers ◽  
Memory B Cells ◽  
Specific Memory ◽  
Specific Amplification ◽  
Antibody Levels ◽  
Red Pulp

Vesicular stomatitis virus (VSV) induces an early T cell-independent neutralizing lgM response that is followed by a long-lived, T cell-dependent lgG response. We used the specific amplification factor of several 100x of VSV-virions for immunohistology to analyze the localization of VSV-specific B cells at different time points after immunization. At the peak of the IgM response (day 4), VSV-specific B cells were predominantly present in the red pulp and marginal zone but not in the T area. These B cells were mostly stained in the cytoplasm, characterizing them as antibody secreting cells. By day 6 after immunization, germinal centers (GC) containing surface-stained VSV-specific B cells became detectable and were fully established by day 12. At the same time, large VSV-specific B cell aggregates were present in the red pulp. High numbers of VSV-specific GC associated with persisting antigen were present 1 mo after immunization and later, i.e., considerably longer than has been observed for haptens. Some GC, exhibiting follicular dendritic cells and containing VSV-specific, proliferating B cells were still detectable up to 100 d after immunization. Long-lived GC were also observed after immunization with recombinant VSV-glycoprotein in absence of adjuvants. Thus some anti-virally protective (memory) B cells are cycling and locally proliferate in long-lived GC in association with persisting antigen and therefore seem responsible for long-term maintenance of elevated antibody levels. These observations extend earlier studies with carrier hapten antigens in adjuvant depots or complexed with specific IgG; they are the first to show colocalization of antigen and specific memory B cells and to analyze a protective neutralizing antibody response against an acute viral infection.

scholarly journals COVID-19 convalescents exhibit deficient humoral and T cell responses to variant of concern Spike antigens at 12 month post-infection

2021 ◽  
Author(s):  
Pablo Garcia-Valtanen ◽  
Christopher Martin Hope ◽  
Makutiro Ghislain Masavuli ◽  
Arthur Eng Lip Yeow ◽  
Harikrishnan Balachandran ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Post Infection ◽  
T Cell Responses ◽  
Memory B Cells ◽  
Pseudotyped Virus ◽  
Cell Responses ◽  
Specific Memory ◽  
Cell Functionality

Background The duration and magnitude of SARS-CoV-2 immunity after infection, especially with regard to the emergence of new variants of concern (VoC), remains unclear. Here, immune memory to primary infection and immunity to VoC was assessed in mild-COVID-19 convalescents one year after infection and in the absence of viral re-exposure or COVID-19 vaccination. Methods Serum and PBMC were collected from mild-COVID-19 convalescents at ~6 and 12 months after a COVID-19 positive PCR (n=43) and from healthy SARS-CoV-2-seronegative controls (n=15-40). Serum titers of RBD and Spike-specific Ig were quantified by ELISA. Virus neutralisation was assessed against homologous, pseudotyped virus and homologous and VoC live viruses. Frequencies of Spike and RBD-specific memory B cells were quantified by flow cytometry. Magnitude of memory T cell responses was quantified and phenotyped by activation-induced marker assay, while T cell functionality was assessed by intracellular cytokine staining using peptides specific to homologous Spike virus antigen and four VoC Spike antigens. Findings At 12 months after mild-COVID-19, >90% of convalescents remained seropositive for RBD-IgG and 88.9% had circulating RBD-specific memory B cells. Despite this, only 51.2% convalescents had serum neutralising activity against homologous live-SARS-CoV-2 virus, which decreased to 44.2% when tested against live B.1.1.7, 4.6% against B.1.351, 11.6% against P.1 and 16.2%, against B.1.617.2 VoC. Spike and non-Spike-specific T cells were detected in >50% of convalescents with frequency values higher for Spike antigen (95% CI, 0.29-0.68% in CD4+ and 0.11-0.35% in CD8+ T cells), compared to non-Spike antigens. Despite the high prevalence and maintenance of Spike-specific T cells in Spike 'high-responder' convalescents at 12 months, T cell functionality, measured by cytokine expression after stimulation with Spike epitopes corresponding to VoC was severely affected. Interpretations SARS-CoV-2 immunity is retained in a significant proportion of mild COVID-19 convalescents 12 months post-infection in the absence of re-exposure to the virus. Despite this, changes in the amino acid sequence of the Spike antigen that are present in current VoC result in virus evasion of neutralising antibodies, as well as evasion of functional T cell responses.

scholarly journals Antigen-Specific B Cell Memory

2000 ◽  
Vol 191 (7) ◽  
pp. 1149-1166 ◽  
Author(s):  
Louise J. McHeyzer-Williams ◽  
Melinda Cool ◽  
Michael G. McHeyzer-Williams
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Memory B Cells ◽  
Cell Memory ◽  
Specific Memory ◽  
B Cell Memory ◽  
Cellular Components

The mechanisms that regulate B cell memory and the rapid recall response to antigen remain poorly defined. This study focuses on the rapid expression of B cell memory upon antigen recall in vivo, and the replenishment of quiescent B cell memory that follows. Based on expression of CD138 and B220, we reveal a unique and major subtype of antigen-specific memory B cells (B220−CD138−) that are distinct from antibody-secreting B cells (B220+/−CD138+) and B220+CD138− memory B cells. These nonsecreting somatically mutated B220− memory responders rapidly dominate the splenic response and comprise >95% of antigen-specific memory B cells that migrate to the bone marrow. By day 42 after recall, the predominant quiescent memory B cell population in the spleen (75–85%) and the bone marrow (>95%) expresses the B220− phenotype. Upon adoptive transfer, B220− memory B cells proliferate to a lesser degree but produce greater amounts of antibody than their B220+ counterparts. The pattern of cellular differentiation after transfer indicates that B220− memory B cells act as stable self-replenishing intermediates that arise from B220+ memory B cells and produce antibody-secreting cells on rechallenge with antigen. Cell surface phenotype and Ig isotype expression divide the B220− compartment into two main subsets with distinct patterns of integrin and coreceptor expression. Thus, we identify new cellular components of B cell memory and propose a model for long-term protective immunity that is regulated by a complex balance of committed memory B cells with subspecialized immune function.

scholarly journals Broad Hemagglutinin-Specific Memory B Cell Expansion by Seasonal Influenza Virus Infection Reflects Early-Life Imprinting and Adaptation to the Infecting Virus

2019 ◽  
Vol 93 (8) ◽  
Author(s):  
Brenda L. Tesini ◽  
Preshetha Kanagaiah ◽  
Jiong Wang ◽  
Megan Hahn ◽  
Jessica L. Halliley ◽  
...  
Keyword(s):  
Influenza Virus ◽  
B Cells ◽  
Virus Infection ◽  
B Cell ◽  
Specific Antibody ◽  
Early Life ◽  
Influenza Virus Infection ◽  
Memory B Cells ◽  
Specific Memory ◽  
Original Antigenic Sin

ABSTRACTMemory B cells (MBCs) are key determinants of the B cell response to influenza virus infection and vaccination, but the effect of different forms of influenza antigen exposure on MBC populations has received little attention. We analyzed peripheral blood mononuclear cells and plasma collected following human H3N2 influenza infection to investigate the relationship between hemagglutinin-specific antibody production and changes in the size and character of hemagglutinin-reactive MBC populations. Infection produced increased concentrations of plasma IgG reactive to the H3 head of the infecting virus, to the conserved stalk, and to a broad chronological range of H3s consistent with original antigenic sin responses. H3-reactive IgG MBC expansion after infection included reactivity to head and stalk domains. Notably, expansion of H3 head-reactive MBC populations was particularly broad and reflected original antigenic sin patterns of IgG production. Findings also suggest that early-life H3N2 infection “imprints” for strong H3 stalk-specific MBC expansion. Despite the breadth of MBC expansion, the MBC response included an increase in affinity for the H3 head of the infecting virus. Overall, our findings indicate that H3-reactive MBC expansion following H3N2 infection is consistent with maintenance of response patterns established early in life, but nevertheless includes MBC adaptation to the infecting virus.IMPORTANCERapid and vigorous virus-specific antibody responses to influenza virus infection and vaccination result from activation of preexisting virus-specific memory B cells (MBCs). Understanding the effects of different forms of influenza virus exposure on MBC populations is therefore an important guide to the development of effective immunization strategies. We demonstrate that exposure to the influenza hemagglutinin via natural infection enhances broad protection through expansion of hemagglutinin-reactive MBC populations that recognize head and stalk regions of the molecule. Notably, we show that hemagglutinin-reactive MBC expansion reflects imprinting by early-life infection and that this might apply to stalk-reactive, as well as to head-reactive, MBCs. Our findings provide experimental support for the role of MBCs in maintaining imprinting effects and suggest a mechanism by which imprinting might confer heterosubtypic protection against avian influenza viruses. It will be important to compare our findings to the situation after influenza vaccination.

scholarly journals A case of Mycobacterium bovis Bacillus Calmette-Guérin (BCG) strain meningitis and ventriculitis following BCG vaccination

2020 ◽  
Vol 100 ◽  
pp. 373-376 ◽  
Author(s):  
Mihoko Furuichi ◽  
Fumi Mori ◽  
Yoji Uejima ◽  
Satoshi Sato ◽  
Jun Kurihara ◽  
...  
Keyword(s):  
Mycobacterium Bovis ◽  
Bacillus Calmette Guerin ◽  
Bcg Vaccination
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