scholarly journals Antibody avidity, persistence, and response to antigen recall: comparison of vaccine adjuvants

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Sonia Budroni ◽  
Francesca Buricchi ◽  
Andrea Cavallone ◽  
Patricia Bourguignon ◽  
Magalie Caubet ◽  
...  
Keyword(s):  
B Cell ◽  
T Cell Response ◽  
High Avidity ◽  
Vaccine Adjuvants ◽  
Adaptive Responses ◽  
Post Dose ◽  
Antibody Avidity ◽  
Antibody Persistence ◽  
Fractional Dose ◽  
Avidity Maturation

AbstractDifferences in innate immune ‘imprinting’ between vaccine adjuvants may mediate dissimilar effects on the quantity/quality of persisting adaptive responses. We compared antibody avidity maturation, antibody/memory B cell/CD4+ T cell response durability, and recall responses to non-adjuvanted fractional-dose antigen administered 1-year post-immunization (Day [D]360), between hepatitis B vaccines containing Adjuvant System (AS)01B, AS01E, AS03, AS04, or Alum (NCT00805389). Both the antibody and B cell levels ranked similarly (AS01B/E/AS03 > AS04 > Alum) at peak response, at D360, and following their increases post-antigen recall (D390). Proportions of high-avidity antibodies increased post-dose 2 across all groups and persisted at D360, but avidity maturation appeared to be more strongly promoted by AS vs. Alum. Post-antigen recall, frequencies of subjects with high-avidity antibodies increased only markedly in the AS groups. Among the AS, total antibody responses were lowest for AS04. However, proportions of high-avidity antibodies were similar between groups, suggesting that MPL in AS04 contributes to avidity maturation. Specific combinations of immunoenhancers in the AS, regardless of their individual nature, increase antibody persistence and avidity maturation.

scholarly journals Vaccination versus infection with SARS‐CoV‐2: Establishment of a high avidity IgG response versus incomplete avidity maturation

2021 ◽  
Author(s):  
Friedhelm Struck ◽  
Patrick Schreiner ◽  
Eva Staschik ◽  
Karin Wochinz‐Richter ◽  
Sarah Schulz ◽  
...  
Keyword(s):  
High Avidity ◽  
Response Versus ◽  
Avidity Maturation

scholarly journals Improved Immune Responses against Zika Virus after Sequential Dengue and Zika Virus Infection in Human

2018 ◽  
Author(s):  
Felix G. Delgado ◽  
Karina I. Torres ◽  
Jaime E. Castellanos ◽  
Consuelo Romero-Sánchez ◽  
Etienne Simon-Lorière ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
B Cell ◽  
Zika Virus ◽  
Neutralizing Antibodies ◽  
Denv Infection ◽  
T Cell Response ◽  
Zikv Infection ◽  
Cell Responses ◽  
B Cell Responses

The high level of dengue virus (DENV) seroprevalence in areas where Zika virus (ZIKV) is circulating and the cross-reactivity between these two viruses have raised concerns on the risk of increased ZIKV disease severity for patients with a history of previous DENV infection. To determine the role of DENV pre-immunity in ZIKV infection, we analysed the T and B cell responses against ZIKV in donors with or without previous DENV infection. Using PBMCs from donors living in an endemic area in Colombia, we have identified, by interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assay, most of the immunodominant ZIKV T-cell epitopes in the non-structural proteins NS1, NS3 and NS5. Analyses of the T and B-cell responses in the same donors revealed a stronger T-cell response against peptides conserved between DENV and ZIKV, with a higher level of ZIKV-neutralizing antibodies in DENV-immune donors, in comparison with DENV-naïve donors. Strikingly, the potential for antibody mediated enhancement of ZIKV infection was reduced in donors with sequential DENV and ZIKV infection in comparison with donors with DENV infection only. Altogether, these data suggest that individuals with DENV immunity present improved immune responses against ZIKV.

scholarly journals Antibody Avidity in Humoral Immune Responses in Bangladeshi Children and Adults following Administration of an Oral Killed Cholera Vaccine

2013 ◽  
Vol 20 (10) ◽  
pp. 1541-1548 ◽  
Author(s):  
Mohammad Murshid Alam ◽  
Daniel T. Leung ◽  
Marjahan Akhtar ◽  
Mohammad Nazim ◽  
Sarmin Akter ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
T Cell Responses ◽  
Memory B Cell ◽  
Antibody Avidity ◽  
Memory T Cell ◽  
Cell Responses ◽  
Specific Memory ◽  
Iga Antibodies ◽  
Specific Igg

ABSTRACTAntibody avidity for antigens following disease or vaccination increases with affinity maturation and somatic hypermutation. In this study, we followed children and adults in Bangladesh for 1 year following oral cholera vaccination and measured the avidity of antibodies to the T cell-dependent antigen cholera toxin B subunit (CTB) and the T cell-independent antigen lipopolysaccharide (LPS) in comparison with responses in other immunological measurements. Children produced CTB-specific IgG and IgA antibodies of high avidity following vaccination, which persisted for several months; the magnitudes of responses were comparable to those seen in adult vaccinees. The avidity of LPS-specific IgG and IgA antibodies in vaccinees increased significantly shortly after the second dose of vaccine but waned rapidly to baseline levels thereafter. CTB-specific memory B cells were present for only a short time following vaccination, and we did not find significant memory B cell responses to LPS in any age group. For older children, there was a significant correlation between CTB-specific memory T cell responses after the second dose of vaccine and CTB-specific IgG antibody avidity indices over the subsequent year. These findings suggest that vaccination induces a longer-lasting increase in the avidity of antibodies to a T cell-dependent antigen than is measured by a memory B cell response to that antigen and that early memory T cell responses correlate well with the subsequent development of higher-avidity antibodies.

Impaired Specific B-Cell While Preserved T-Cell Response Against Influenza Vaccine in SOT Recipients.

2014 ◽  
Vol 98 ◽  
pp. 188
Author(s):  
D. Zbinden ◽  
M. Pascual ◽  
S. Lartey ◽  
R. Pathirana ◽  
G. Bredholt ◽  
...  
Keyword(s):  
T Cell ◽  
Influenza Vaccine ◽  
B Cell ◽  
Cell Response ◽  
T Cell Response

scholarly journals Active PI3K abrogates central tolerance in high-avidity autoreactive B cells

2019 ◽  
Vol 216 (5) ◽  
pp. 1135-1153 ◽  
Author(s):  
Sarah A. Greaves ◽  
Jacob N. Peterson ◽  
Pamela Strauch ◽  
Raul M. Torres ◽  
Roberta Pelanda
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Peripheral Tolerance ◽  
High Avidity ◽  
Cell Tolerance ◽  
B Cell Tolerance ◽  
Central Tolerance ◽  
Autoreactive B Cells ◽  
Self Antigen

Autoreactive B cells that bind self-antigen with high avidity in the bone marrow undergo mechanisms of central tolerance that prevent their entry into the peripheral B cell population. These mechanisms are breached in many autoimmune patients, increasing their risk of B cell–mediated autoimmune diseases. Resolving the molecular pathways that can break central B cell tolerance could therefore provide avenues to diminish autoimmunity. Here, we show that B cell–intrinsic expression of a constitutively active form of PI3K-P110α by high-avidity autoreactive B cells of mice completely abrogates central B cell tolerance and further promotes these cells to escape from the bone marrow, differentiate in peripheral tissue, and undergo activation in response to self-antigen. Upon stimulation with T cell help factors, these B cells secrete antibodies in vitro but remain unable to secrete autoantibodies in vivo. Overall, our data demonstrate that activation of the PI3K pathway leads high-avidity autoreactive B cells to breach central, but not late, stages of peripheral tolerance.

scholarly journals Mechanisms behind Functional Avidity Maturation in T Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Marina Rode von Essen ◽  
Martin Kongsbak ◽  
Carsten Geisler
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Somatic Hypermutation ◽  
Cell Receptor ◽  
Affinity Maturation ◽  
Functional Avidity ◽  
Cell Clones ◽  
Genes Encoding ◽  
Avidity Maturation

During an immune response antigen-primed B-cells increase their antigen responsiveness by affinity maturation mediated by somatic hypermutation of the genes encoding the antigen-specific B-cell receptor (BCR) and by selection of higher-affinity B cell clones. Unlike the BCR, the T-cell receptor (TCR) cannot undergo affinity maturation. Nevertheless, antigen-primed T cells significantly increase their antigen responsiveness compared to antigen-inexperienced (naïve) T cells in a process called functional avidity maturation. This paper covers studies that describe differences in T-cell antigen responsiveness during T-cell differentiation along with examples of the mechanisms behind functional avidity maturation in T cells.

scholarly journals Safety Profile of a Virus-Like Particle-Based Vaccine Targeting Self-Protein Interleukin-5 in Horses

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 213 ◽  
Author(s):  
Sigridur Jonsdottir ◽  
Victoria Fettelschoss ◽  
Florian Olomski ◽  
Stephanie C. Talker ◽  
Jelena Mirkovitch ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Mononuclear Cells ◽  
Clinical Signs ◽  
T Cell Response ◽  
Type I ◽  
Cell Responses ◽  
Virus Like Particle ◽  
Ifn Γ

Background: Insect bite hypersensitivity (IBH) is an eosinophilic allergic dermatitis of horses caused by type I/IVb reactions against mainly Culicoides bites. The vaccination of IBH-affected horses with equine IL-5 coupled to the Cucumber mosaic virus-like particle (eIL-5-CuMVTT) induces IL-5-specific auto-antibodies, resulting in a significant reduction in eosinophil levels in blood and clinical signs. Objective: the preclinical and clinical safety of the eIL-5-CuMVTT vaccine. Methods: The B cell responses were assessed by longitudinal measurement of IL-5- and CuMVTT-specific IgG in the serum and plasma of vaccinated and unvaccinated horses. Further, peripheral blood mononuclear cells (PBMCs) from the same horses were re-stimulated in vitro for the proliferation and IFN-γ production of specific T cells. In addition, we evaluated longitudinal kidney and liver parameters and the general blood status. An endogenous protein challenge was performed in murine IL-5-vaccinated mice. Results: The vaccine was well tolerated as assessed by serum and cellular biomarkers and also induced reversible and neutralizing antibody titers in horses and mice. Endogenous IL-5 stimulation was unable to re-induce anti-IL-5 production. The CD4+ T cells of vaccinated horses produced significantly more IFN-γ and showed a stronger proliferation following stimulation with CuMVTT as compared to the unvaccinated controls. Re-stimulation using E. coli-derived proteins induced low levels of IFNγ+CD4+ cells in vaccinated horses; however, no IFN-γ and proliferation were induced following the HEK-eIL-5 re-stimulation. Conclusions: Vaccination using eIL-5-CuMVTT induces a strong B-cell as well as CuMVTT-specific T cell response without the induction of IL-5-specific T cell responses. Hence, B-cell unresponsiveness against self-IL-5 can be bypassed by inducing CuMVTT carrier-specific T cells, making the vaccine a safe therapeutic option for IBH-affected horses.

scholarly journals A reverse translational study on the effect of rituximab, rituximab plus belimumab, or bortezomib on the humoral autoimmune response in SLE

Rheumatology ◽  
2020 ◽  
Vol 59 (10) ◽  
pp. 2734-2745 ◽  
Author(s):  
Laura S van Dam ◽  
Zgjim Osmani ◽  
Sylvia W A Kamerling ◽  
Tineke Kraaij ◽  
Jaap A   Bakker ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Randomized Clinical Trials ◽  
Ex Vivo ◽  
Neutrophil Extracellular Trap ◽  
Autoimmune Response ◽  
High Avidity ◽  
Trap Formation ◽  
Extracellular Trap ◽  
The Impact

Abstract Objectives SLE is a severe autoimmune disease characterized by autoreactive B cells and IC formation, which causes systemic inflammation. B cell–targeted therapy could be a promising treatment strategy in SLE patients; nevertheless, randomized clinical trials have not always been successful. However, some groups have demonstrated beneficial effects in severe SLE patients with off-label rituximab (RTX) with belimumab (BLM), or bortezomib (BTZ), which targeted different B cells subsets. This study assembled sera from SLE cohorts treated with RTX+BLM (n = 15), BTZ (n = 11) and RTX (n = 16) to get an in-depth insight into the immunological effects of these therapies on autoantibodies and IC formation. Methods Autoantibodies relevant for IC formation and the avidity of anti-dsDNA were determined by ELISA. IC-mediated inflammation was studied by complement levels and ex vivo serum-induced neutrophil extracellular trap formation. Results Reductions in autoantibodies were observed after all approaches, but the spectrum differed depending upon the treatment. Specifically, only RTX+BLM significantly decreased anti-C1q. Achieving seronegativity of ≥1 autoantibody, specifically anti-C1q, was associated with lower disease activity. In all SLE patients, the majority of anti-dsDNA autoantibodies had low avidity. RTX+BLM significantly reduced low-, medium- and high-avidity anti-dsDNA, while RTX and BTZ only significantly reduced medium avidity. IC-mediated inflammation, measured by C3 levels and neutrophil extracellular trap formation, improved after RTX+BLM and RTX but less after BTZ. Conclusion This study demonstrated the impact of different B cell–targeted strategies on autoantibodies and IC formation and their potential clinical relevance in SLE.

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