scholarly journals Differential T- and B-Cell Responses to Pertussis in Acellular Vaccine-Primed versus Whole-Cell Vaccine-Primed Children 2 Years after Preschool Acellular Booster Vaccination

2013 ◽  
Vol 20 (9) ◽  
pp. 1388-1395 ◽  
Author(s):  
Rose-Minke Schure ◽  
Lotte H. Hendrikx ◽  
Lia G. H. de Rond ◽  
Kemal Öztürk ◽  
Elisabeth A. M. Sanders ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Immune Responses ◽  
B Cell ◽  
Booster Vaccination ◽  
Memory B Cells ◽  
Vaccine Antigen ◽  
Whole Cell ◽  
Cell Responses

ABSTRACTThis study investigated long-term cellular and humoral immunity against pertussis after booster vaccination of 4-year-old children who had been vaccinated at 2, 3, 4, and 11 months of age with either whole-cell pertussis (wP) or acellular pertussis (aP) vaccine. Immune responses were evaluated until 2 years after the preschool booster aP vaccination. In a cross-sectional study (registered trial no. ISRCTN65428640), blood samples were taken from wP- and aP-primed children prebooster and 1 month and 2 years postbooster. Pertussis vaccine antigen-specific IgG levels, antibody avidities, and IgG subclasses, as well as T-cell cytokine levels, were measured by fluorescent bead-based multiplex immunoassays. The numbers of pertussis-specific memory B cells and gamma interferon (IFN-γ)-producing T cells were quantified by enzyme-linked immunosorbent spot assays. Even 2 years after booster vaccination, memory B cells were still present and higher levels of pertussis-specific antibodies than prebooster were found in aP-primed children and, to a lesser degree, also in wP-primed children. The antibodies consisted mainly of the IgG1 subclass but also showed an increased IgG4 portion, primarily in the aP-primed children. The antibody avidity indices for pertussis toxin and pertactin in aP-primed children were already high prebooster and remained stable at 2 years, whereas those in wP-primed children increased. All measured prebooster T-cell responses in aP-primed children were already high and remained at similar levels or even decreased during the 2 years after booster vaccination, whereas those in wP-primed children increased. Since the Dutch wP vaccine has been replaced by aP vaccines, the induction of B-cell and T-cell memory immune responses has been enhanced, but antibody levels still wane after five aP vaccinations. Based on these long-term immune responses, the Dutch pertussis vaccination schedule can be optimized, and we discuss here several options.

scholarly journals Ectopic Lymphoid Follicles in Multiple Sclerosis: Centers for Disease Control?

2020 ◽  
Vol 11 ◽  
Author(s):  
Austin Negron ◽  
Olaf Stüve ◽  
Thomas G. Forsthuber
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
T Cell Responses ◽  
Memory B Cells ◽  
Lymphoid Follicles ◽  
Cell Responses ◽  
B Cell Responses

While the contribution of autoreactive CD4+ T cells to the pathogenesis of Multiple Sclerosis (MS) is widely accepted, the advent of B cell-depleting monoclonal antibody (mAb) therapies has shed new light on the complex cellular mechanisms underlying MS pathogenesis. Evidence supports the involvement of B cells in both antibody-dependent and -independent capacities. T cell-dependent B cell responses originate and take shape in germinal centers (GCs), specialized microenvironments that regulate B cell activation and subsequent differentiation into antibody-secreting cells (ASCs) or memory B cells, a process for which CD4+ T cells, namely follicular T helper (TFH) cells, are indispensable. ASCs carry out their effector function primarily via secreted Ig but also through the secretion of both pro- and anti-inflammatory cytokines. Memory B cells, in addition to being capable of rapidly differentiating into ASCs, can function as potent antigen-presenting cells (APCs) to cognate memory CD4+ T cells. Aberrant B cell responses are prevented, at least in part, by follicular regulatory T (TFR) cells, which are key suppressors of GC-derived autoreactive B cell responses through the expression of inhibitory receptors and cytokines, such as CTLA4 and IL-10, respectively. Therefore, GCs represent a critical site of peripheral B cell tolerance, and their dysregulation has been implicated in the pathogenesis of several autoimmune diseases. In MS patients, the presence of GC-like leptomeningeal ectopic lymphoid follicles (eLFs) has prompted their investigation as potential sources of pathogenic B and T cell responses. This hypothesis is supported by elevated levels of CXCL13 and circulating TFH cells in the cerebrospinal fluid (CSF) of MS patients, both of which are required to initiate and maintain GC reactions. Additionally, eLFs in post-mortem MS patient samples are notably devoid of TFR cells. The ability of GCs to generate and perpetuate, but also regulate autoreactive B and T cell responses driving MS pathology makes them an attractive target for therapeutic intervention. In this review, we will summarize the evidence from both humans and animal models supporting B cells as drivers of MS, the role of GC-like eLFs in the pathogenesis of MS, and mechanisms controlling GC-derived autoreactive B cell responses in MS.

Impact of Autologous Dendritic Cell Immunotherapy (Arcelis™) on B Cell Subsets in HIV-1-Infected Subjects Receiving Antiretroviral Therapy

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 80-80
Author(s):  
Mohamed-Rachid Boulassel ◽  
Bader Yassine-Diab ◽  
Don Healey ◽  
Charles Nicolette ◽  
Rafick-Pierre Sékaly ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Immune Responses ◽  
B Cell ◽  
Plasma Cells ◽  
Cell Subset ◽  
Cd8 T Cell ◽  
Memory B Cells ◽  
B Cell Subsets ◽  
Hiv 1

Abstract We demonstrated the enhancement of CD8-specific responses following the administration of an immune-based therapy consisting of dendritic cells (DC) electroporated with autologous amplified HIV-1 RNA and CD40 ligand (CD40 L) RNA manufactured by the Arcelis™ process in HIV patients receiving antiretroviral therapy (ART). We conducted a sub study on circulating B cell populations to further assess changes induced by this autologous DC therapy as CD40L is a major B cell co-stimulatory factor. To this end, we assessed B cell subset changes in relation to the proliferative capacity of CD4+ and CD8+ T cells response to DC targets containing the 4 HIV-1 antigens (Gag, Vpr, Rev, Nef). The co-expression of CD19, CD38, IgD, CD10, CD23, CD27, CD5, and CD138 were analyzed by multi-parametric flow cytometry to assess circulating B cell subsets such as naïve resting B-cells (Bm1), activated naïve B cells (Bm2), GC founder cells (Bm2’), centroblasts and centrocytes (Bm3 and Bm4), early memory B cells (eBm5), memory B cells (Bm5), IgD memory cells, plasma cells, and B-1 cells. Changes in B cells subsets were analyzed before and after the four intradermal injections of this immunotherapeutic product containing 1.2 × 107 DC. Ten ART treated subjects with undetectable viral load (< 50 copies/ml), median CD4+ count of 440 cells/μl (range: 316–1102), and with a CD4+ nadir > 200 cells/μl were studied. Throughout the study, no significant changes in CD4+ cell count, CD4/CD8 ratio, and no viral blips were noticed. The percentage of total B cells, Bm1, Bm2, Bm2′, eBm5, IgD memory, plasma cells, and B-1 cell subsets did not significantly change. However, a decrease in the percentage of Bm3 and Bm4 cells was found (0.36 [0.06–0.86] versus 0.11 [0.04–0.36]; P=0.05). Conversely, an important increase in the Bm5 cell subset was evidenced (10.4 [1.6–24.2] versus 18.1 [5.1–27.5]; P=0.005) suggesting a proliferation of B memory cells induced by DC immunization. In addition, the multifunctional and polyvalent CD8+ T cell proliferative responses to the 4 HIV genes used in this immunotherapy were noticed in 8 out of 9 subjects available for analysis and characterized by an effector memory phenotype. No CD4+ T cell immune responses were detected, consistent with the endogenous HLA class I loading of the antigens. Collectively, these results indicate that this immunotherapy induces an increase in the B memory cell population in the absence of inducing any clinically apparent autoimmunity along with strong HIV specific multifunctional CD8+ T cell specific immune responses.

scholarly journals SARS-CoV-2 Vaccine Induced Atypical Immune Responses in Antibody Defects: Everybody Does their Best

2021 ◽  
Author(s):  
Ane Fernandez Salinas ◽  
Eva Piano Mortari ◽  
Sara Terreri ◽  
Concetta Quintarelli ◽  
Federica Pulvirenti ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Immune Responses ◽  
Vaccine Dose ◽  
Memory B Cells ◽  
Cell Responses ◽  
Specific Memory ◽  
Immune Deficiencies ◽  
Iga Antibody ◽  
Specific Igg

Abstract Background Data on immune responses to SARS-CoV-2 in patients with Primary Antibody Deficiencies (PAD) are limited to infected patients and to heterogeneous cohorts after immunization. Methods Forty-one patients with Common Variable Immune Deficiencies (CVID), six patients with X-linked Agammaglobulinemia (XLA), and 28 healthy age-matched controls (HD) were analyzed for anti-Spike and anti-receptor binding domain (RBD) antibody production, generation of Spike-specific memory B-cells, and Spike-specific T-cells before vaccination and one week after the second dose of BNT162b2 vaccine. Results The vaccine induced Spike-specific IgG and IgA antibody responses in all HD and in 20% of SARS-CoV-2 naive CVID patients. Anti-Spike IgG were detectable before vaccination in 4 out 7 CVID previously infected with SARS-CoV-2 and were boosted in six out of seven patients by the subsequent immunization raising higher levels than patients naïve to infection. While HD generated Spike-specific memory B-cells, and RBD-specific B-cells, CVID generated Spike-specific atypical B-cells, while RBD-specific B-cells were undetectable in all patients, indicating the incapability to generate this new specificity. Specific T-cell responses were evident in all HD and defective in 30% of CVID. All but one patient with XLA responded by specific T-cell only. Conclusion In PAD patients, early atypical immune responses after BNT162b2 immunization occurred, possibly by extra-follicular or incomplete germinal center reactions. If these responses to vaccination might result in a partial protection from infection or reinfection is now unknown. Our data suggests that SARS-CoV-2 infection more effectively primes the immune response than the immunization alone, possibly suggesting the need for a third vaccine dose for patients not previously infected.

scholarly journals BAFFR controls early memory B cell responses but is dispensable for germinal center function

2020 ◽  
Vol 218 (2) ◽  
Author(s):  
Angelica W.Y. Lau ◽  
Vivian M. Turner ◽  
Katherine Bourne ◽  
Jana R. Hermes ◽  
Tyani D. Chan ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Germinal Center ◽  
Memory B Cells ◽  
Term Survival ◽  
Cell Responses ◽  
Tnf Superfamily ◽  
Surface Receptor ◽  
Early Memory

The TNF superfamily ligand BAFF maintains the survival of naive B cells by signaling through its surface receptor, BAFFR. Activated B cells maintain expression of BAFFR after they differentiate into germinal center (GC) or memory B cells (MBCs). However, the functions of BAFFR in these antigen-experienced B cell populations remain unclear. Here, we show that B cell–intrinsic BAFFR does not play a significant role in the survival or function of GC B cells or in the generation of the somatically mutated MBCs derived from them. Instead, BAFF/BAFFR signaling was required to generate the unmutated, GC-independent MBCs that differentiate directly from activated B cell blasts early in the response. Furthermore, amplification of BAFFR signaling in responding B cells did not affect GCs or the generation of GC-derived MBCs but greatly expanded the GC-independent MBC response. Although BAFF/BAFFR signaling specifically controlled the formation of the GC-independent MBC response, both types of MBCs required input from this pathway for optimal long-term survival.

scholarly journals Immunity in Omicron SARS-CoV-2 breakthrough COVID-19 in vaccinated adults

2022 ◽  
Author(s):  
Hassen Kared ◽  
Asia-Sophia Fumika Michaela Wolf ◽  
Amin Alirezaylavasani ◽  
Anthony Ravussin ◽  
Guri Solum ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Cell ◽  
De Novo ◽  
T Cell Responses ◽  
Affinity Maturation ◽  
T Cell Response ◽  
Memory B Cells ◽  
Viral Escape ◽  
Cell Responses

The new SARS-CoV-2 variant of concern (VOC) Omicron has more than 30 mutations in the receptor binding domain (RBD) of the Spike protein enabling viral escape from antibodies in vaccinated individuals and increased transmissibility. It is unclear how vaccine immunity protects against Omicron infection. Here we show that vaccinated participants at a superspreader event had robust recall response of humoral and pre-existing cellular immunity induced by the vaccines, and an emergent de novo T cell response to non-Spike antigens. We compared cases from a Christmas party where 81 of 110 (74%) developed Omicron breakthrough COVID-19, with Delta breakthrough cases and vaccinated non-infected controls. Omicron cases had significantly increased activated SARS-CoV-2 wild type Spike-specific (vaccine) cytotoxic T cells, activated follicular helper (TFH) cells, functional T cell responses, boosted humoral responses, activated anti-Spike plasmablasts and anti-RBD memory B cells compared to controls. Omicron cases had significantly increased de novo memory T cell responses to non-Spike viral antigens compared to Delta breakthrough cases demonstrating development of broad immunity. The rapid release of Spike and RBD-specific IgG+ B cell plasmablasts and memory B cells into circulation suggested affinity maturation of antibodies and that concerted T and B cell immunity may provide durable broad immunity.

CRM197-conjugated serogroup C meningococcal capsular polysaccharide, but not the native polysaccharide, induces persistent antigen-specific memory B cells

Blood ◽  
2006 ◽  
Vol 108 (8) ◽  
pp. 2642-2647 ◽  
Author(s):  
Dominic F. Kelly ◽  
Mathew D. Snape ◽  
Elizabeth A. Clutterbuck ◽  
Sarah Green ◽  
Claire Snowden ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Conjugate Vaccine ◽  
Polysaccharide Vaccine ◽  
Memory B Cells ◽  
Immunologic Memory ◽  
Memory B Cell ◽  
Cell Responses ◽  
Glycoconjugate Vaccine

Abstract Neisseria meningitidis is one of the leading causes of bacterial meningitis and septicemia in children. Vaccines containing the purified polysaccharide capsule from the organism, a T cell-independent antigen, have been available for decades but do not appear to provide protection in infancy or immunologic memory as measured by antibody responses. By contrast, T cell-dependent serogroup C protein-polysaccharide conjugate vaccines protect against serogroup C meningococcal disease from infancy onward and prime for immunologic memory. We compared the magnitude and kinetics of plasma cell and memory B-cell responses to a meningococcal plain polysaccharide vaccine and a serogroup C glycoconjugate vaccine in adolescents previously primed with the conjugate vaccine. Plasma cell kinetics were similar for both vaccines, though the magnitude of the response was greater for the glycoconjugate. In contrast to the glycoconjugate vaccine, the plain polysaccharide vaccine did not induce a persistent immunoglobulin G (IgG) memory B-cell response. This is the first study to directly show that serogroup C meningococcal glycoconjugate vaccines induce persistent production of memory B cells and that plain polysaccharide vaccines do not, supporting the use of the conjugate vaccine for sustained population protection. Detection of peripheral blood memory B-cell responses after vaccination may be a useful signature of successful induction of immunologic memory during novel vaccine evaluation.

scholarly journals B Cell Response Induced by SARS-CoV-2 Infection Is Boosted by the BNT162b2 Vaccine in Primary Antibody Deficiencies

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2915
Author(s):  
Federica Pulvirenti ◽  
Ane Fernandez Salinas ◽  
Cinzia Milito ◽  
Sara Terreri ◽  
Eva Piano Mortari ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Response ◽  
T Cell Responses ◽  
Memory B Cells ◽  
Primary Antibody ◽  
Cell Responses ◽  
Primary Antibody Deficiencies ◽  
Specific Memory

Background: Patients with primary antibody deficiencies are at risk in the current COVID-19 pandemic due to their impaired response to infection and vaccination. Specifically, patients with common variable immunodeficiency (CVID) generated poor spike-specific antibody and T cell responses after immunization. Methods: Thirty-four CVID convalescent patients after SARS-CoV-2 infection, 38 CVID patients immunized with two doses of the BNT162b2 vaccine, and 20 SARS-CoV-2 CVID convalescents later and immunized with BNT162b2 were analyzed for the anti-spike IgG production and the generation of spike-specific memory B cells and T cells. Results: Spike-specific IgG was induced more frequently after infection than after vaccination (82% vs. 34%). The antibody response was boosted in convalescents by vaccination. Although immunized patients generated atypical memory B cells possibly by extra-follicular or incomplete germinal center reactions, convalescents responded to infection by generating spike-specific memory B cells that were improved by the subsequent immunization. Poor spike-specific T cell responses were measured independently from the immunological challenge. Conclusions: SARS-CoV-2 infection primed a more efficient classical memory B cell response, whereas the BNT162b2 vaccine induced non-canonical B cell responses in CVID. Natural infection responses were boosted by subsequent immunization, suggesting the possibility to further stimulate the immune response by additional vaccine doses in CVID.

scholarly journals T-independent type II immune responses generate memory B cells

2006 ◽  
Vol 203 (2) ◽  
pp. 305-310 ◽  
Author(s):  
Tetyana V. Obukhanych ◽  
Michel C. Nussenzweig
Keyword(s):  
B Cells ◽  
Immune Responses ◽  
B Cell ◽  
Memory B Cells ◽  
Type Ii ◽  
Immunologic Memory ◽  
Protein Antigens ◽  
Cell Responses ◽  
Specific Immunoglobulin ◽  
Polysaccharide Antigens

Unlike T-dependent immune responses against protein antigens, T-independent responses against polysaccharides confer long-lasting humoral immunity in the absence of recall responses and are not known to generate memory B cells. Here we report that polysaccharide antigens elicit memory B cells that are phenotypically distinct from those elicited by protein antigens. Furthermore, memory B cell responses against polysaccharides are regulated by antigen-specific immunoglobulin G antibodies. As the generation and regulation of immunologic memory is central to vaccination, our findings help explain the mode of action of the few existing polysaccharide vaccines and provide a rationale for a wider application of polysaccharide-based strategies in vaccination.

scholarly journals SIV infection of rhesus macaques results in dysfunctional T- and B-cell responses to neo and recall Leishmania major vaccination

Blood ◽  
2011 ◽  
Vol 118 (22) ◽  
pp. 5803-5812 ◽  
Author(s):  
Nichole R. Klatt ◽  
Carol L. Vinton ◽  
Rebecca M. Lynch ◽  
Lauren A. Canary ◽  
Jason Ho ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Immune Responses ◽  
Leishmania Major ◽  
Rhesus Macaques ◽  
Memory B Cells ◽  
Cell Responses ◽  
Follicular Helper ◽  
Siv Infection

Abstract HIV infection is characterized by immune system dysregulation, including depletion of CD4+ T cells, immune activation, and abnormal B- and T-cell responses. However, the immunologic mechanisms underlying lymphocytic dysfunctionality and whether it is restricted to immune responses against neo antigens, recall antigens, or both is unclear. Here, we immunized SIV-infected and uninfected rhesus macaques to induce immune responses against neo and recall antigens using a Leishmania major polyprotein (MML) vaccine given with poly-ICLC adjuvant. We found that vaccinated SIVuninfected animals induced high frequencies of polyfunctional MML-specific CD4+ T cells. However, in SIV-infected animals, CD4+ T-cell functionality decreased after both neo (P = .0025) and recall (P = .0080) MML vaccination. Furthermore, after SIV infection, the frequency of MML-specific antibody-secreting classic memory B cells was decreased compared with vaccinated, SIV-uninfected animals. Specifically, antibody-secreting classic memory B cells that produced IgA in response to either neo (P = .0221) or recall (P = .0356) MML vaccinations were decreased. Furthermore, we found that T-follicular helper cells, which are essential for priming B cells, are preferentially infected with SIV. These data indicate that SIV infection results in dysfunctional T-cell responses to neo and recall vaccinations, and direct SIV infection of T-follicular helper cells, both of which probably contribute to deficient B-cell responses and, presumably, susceptibility to certain opportunistic infections.

scholarly journals The presence of circulating antibody secreting cells and long-lived memory B cell responses to reticulocyte binding protein 1a in Plasmodium vivax patients

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Piyawan Kochayoo ◽  
Pattarawan Sanguansuttikul ◽  
Pongsakorn Thawornpan ◽  
Kittikorn Wangriatisak ◽  
John H. Adams ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Memory B Cells ◽  
Antibody Responses ◽  
Blood Stage ◽  
Memory B Cell ◽  
Cell Responses ◽  
Antibody Titers ◽  
B Cell Responses

Abstract Background Development of an effective vaccine against blood-stage malaria requires the induction of long-term immune responses. Plasmodium vivax Reticulocyte Binding Protein 1a (PvRBP1a) is a blood-stage parasite antigen which is associated with invasion of red blood cells and induces antibody responses. Thus, PvRBP1a is considered as a target for design of a blood-stage vaccine against vivax malaria. Methods Both cross-sectional and cohort studies were used to explore the development and persistence of long-lived antibody and memory B cell responses to PvRBP1a in individuals who lived in an area of low malaria endemicity. Antibody titers and frequency of memory B cells specific to PvRBP1a were measured during infection and following recovery for up to 12 months. Results IgG antibody responses against PvRBP1a were prevalent during acute vivax malaria, predominantly IgG1 subclass responses. High responders to PvRBP1a had persistent antibody responses for at least 12-month post-infection. Further analysis of high responder found a direct relation between antibody titers and frequency of activated and atypical memory B cells. Furthermore, circulating antibody secreting cells and memory B cells specific to PvRBP1a were generated during infection. The PvRBP1a-specific memory B cells were maintained for up to 3-year post-infection, indicating the ability of PvRBP1a to induce long-term humoral immunity. Conclusion The study revealed an ability of PvRBP1a protein to induce the generation and maintenance of antibody and memory B cell responses. Therefore, PvRBP1a could be considered as a vaccine candidate against the blood-stage of P. vivax.

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