scholarly journals Divergent SARS-CoV-2-specific T and B cell responses in severe but not mild COVID-19

2020 ◽  
Author(s):  
Anna E. Oja ◽  
Anno Saris ◽  
Cherien A. Ghandour ◽  
Natasja A.M. Kragten ◽  
Boris M. Hogema ◽  
...  
Keyword(s):  
Immune Responses ◽  
B Cell ◽  
Critically Ill ◽  
Clinical Presentation ◽  
Therapeutic Interventions ◽  
Igg Antibody ◽  
Cell Responses ◽  
Specific Igg ◽  
B Cell Responses ◽  
Mild Clinical Presentation

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current coronavirus disease 2019 (COVID-19) pandemic. Understanding both the immunological processes providing specific immunity and potential immunopathology underlying the pathogenesis of this disease may provide valuable insights for potential therapeutic interventions. Here, we quantified SARS-CoV-2 specific immune responses in patients with different clinical courses. Compared to individuals with a mild clinical presentation, CD4+ T cell responses were qualitatively impaired in critically ill patients. Strikingly, however, in these patients the specific IgG antibody response was remarkably strong. The observed disparate T and B cell responses could be indicative of a deregulated immune response in critically ill COVID-19 patients.

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 Parenteral Vaccination with a Cholera Conjugate Vaccine Boosts Vibriocidal and Anti-OSP Responses in Mice Previously Immunized with an Oral Cholera Vaccine

2021 ◽  
Author(s):  
Aklima Akter ◽  
Meagan Kelly ◽  
Richelle C. Charles ◽  
Jason B. Harris ◽  
Stephen B. Calderwood ◽  
...  
Keyword(s):  
Immune Responses ◽  
B Cell ◽  
Conjugate Vaccine ◽  
Oral Vaccine ◽  
Cholera Vaccine ◽  
Memory B Cell ◽  
Cell Responses ◽  
Oral Cholera Vaccine ◽  
B Cell Responses ◽  
Cholera Vaccination

Oral cholera vaccination protects against cholera; however, responses in young children are low and of short duration. The best current correlates of protection against cholera target Vibrio cholerae O-specific polysaccharide (anti-OSP), including vibriocidal responses. A cholera conjugate vaccine has been developed that induces anti-OSP immune responses, including memory B-cell responses. To address whether cholera conjugate vaccine would boost immune responses following oral cholera vaccination, we immunized mice with oral cholera vaccine Inaba CVD 103-HgR or buffer only (placebo) on day 0, followed by parenteral boosting immunizations on days 14, 42, and 70 with cholera conjugate vaccine Inaba OSP: recombinant tetanus toxoid heavy chain fragment or PBS/placebo. Compared with responses in mice immunized with oral vaccine alone or intramuscular cholera conjugate vaccine alone, mice receiving combination vaccination developed significantly higher vibriocidal, IgM OSP-specific serum responses and OSP-specific IgM memory B-cell responses. A combined vaccination approach, which includes oral cholera vaccination followed by parenteral cholera conjugate vaccine boosting, results in increased immune responses that have been associated with protection against cholera. These results suggest that such an approach should be evaluated in humans.

scholarly journals Conserved Regions from Neisseria gonorrhoeae Pilin Are Immunosilent and Not Immunosuppressive

2007 ◽  
Vol 75 (8) ◽  
pp. 4138-4147 ◽  
Author(s):  
Johanna K. Hansen ◽  
Karen P. Demick ◽  
John M. Mansfield ◽  
Katrina T. Forest
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Neisseria Gonorrhoeae ◽  
B Cell ◽  
Hypervariable Region ◽  
Suppressor Cell ◽  
Dimensional Structure ◽  
Cell Responses ◽  
Conserved Regions ◽  
B Cell Responses

ABSTRACT PilE is the primary subunit of type IV pili from Neisseria gonorrhoeae and contains a surface-exposed hypervariable region thought to be one feature of pili that has prevented development of a pilin-based vaccine. We have created a three-dimensional structure-based antigen by replacing the hypervariable region of PilE with an aspartate-glutamine linker chosen from the sequence of Pseudomonas aeruginosa PilA. We then characterized murine immune responses to this novel protein to determine if conserved PilE regions could serve as a vaccine candidate. The control PilE protein elicited strong T-cell-dependent B-cell responses that are specific to epitopes in both the hypervariable deletion and control proteins. In contrast, the hypervariable deletion protein was unable to elicit an immune response in mice, suggesting that in the absence of the hypervariable region, the conserved regions of PilE alone are not sufficient for antibody production. Further analysis of these PilE proteins with suppressor cell assays showed that neither suppresses T- or B-cell responses, and flow cytometry experiments suggested that they do not exert suppressor effects by activating T regulatory cells. Our results show that in the murine model, the hypervariable region of PilE is required to activate immune responses to pilin, whereas the conserved regions are unusually nonimmunogenic. In addition, we show that both hypervariable and conserved regions of pilin are not suppressive, suggesting that PilE does not cause the decrease in T-cell populations observed during gonococcal cervicitis.

scholarly journals Study of Avidity of Antigen-Specific Antibody as a Means of Understanding Development of Long-Term Immunological Memory after Vibrio cholerae O1 Infection

2012 ◽  
Vol 20 (1) ◽  
pp. 17-23 ◽  
Author(s):  
Mohammad Murshid Alam ◽  
Mohammad Arifuzzaman ◽  
Shaikh Meshbahuddin Ahmad ◽  
M. Ismail Hosen ◽  
Mohammad Arif Rahman ◽  
...  
Keyword(s):  
B Cell ◽  
Vibrio Cholerae ◽  
Memory B Cell ◽  
Content Type ◽  
Cell Responses ◽  
Specific Memory ◽  
Iga Antibodies ◽  
Specific Igg ◽  
B Cell Responses

ABSTRACTThe avidity of antibodies to specific antigens and the relationship of avidity to memory B cell responses to these antigens have not been studied in patients with cholera or those receiving oral cholera vaccines. We measured the avidity of antibodies to cholera toxin B subunit (CTB) andVibrio choleraeO1 lipopolysaccharide (LPS) in Bangladeshi adult cholera patients (n= 30), as well as vaccinees (n= 30) after administration of two doses of a killed oral cholera vaccine. We assessed antibody and memory B cell responses at the acute stage in patients or prior to vaccination in vaccinees and then in follow-up over a year. Both patients and vaccinees mounted CTB-specific IgG and IgA antibodies of high avidity. Patients showed longer persistence of these antibodies than vaccinees, with persistence lasting in patients up to day 270 to 360. The avidity of LPS-specific IgG and IgA antibodies in patients remained elevated up to 180 days of follow-up. Vaccinees mounted highly avid LPS-specific antibodies at day 17 (3 days after the second dose of vaccine), but the avidity waned rapidly to baseline by 30 days. We examined the correlation between antigen-specific memory B cell responses and avidity indices for both antigens. We found that numbers of CTB- and LPS-specific memory B cells significantly correlated with the avidity indices of the corresponding antibodies (P< 0.05; Spearman'sρ= 0.28 to 0.45). These findings suggest that antibody avidity after infection and immunization is a good correlate of the development and maintenance of memory B cell responses toVibrio choleraeO1 antigens.

scholarly journals B-Cell Responses to Intramuscular Administration of a Bivalent Virus-Like Particle Human Norovirus Vaccine

2017 ◽  
Vol 24 (5) ◽  
Author(s):  
Sasirekha Ramani ◽  
Frederick H. Neill ◽  
Jennifer Ferreira ◽  
John J. Treanor ◽  
Sharon E. Frey ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cellular Immunity ◽  
Memory B Cells ◽  
Intramuscular Administration ◽  
Correlate Of Protection ◽  
Cell Responses ◽  
Virus Like Particle ◽  
Specific Igg ◽  
B Cell Responses

ABSTRACT Human noroviruses (HuNoVs) are a leading cause of acute gastroenteritis worldwide. A virus-like particle (VLP) candidate vaccine induces the production of serum histo-blood group antigen (HBGA)-blocking antibodies, the first identified correlate of protection from HuNoV gastroenteritis. Recently, virus-specific IgG memory B cells were identified to be another potential correlate of protection against HuNoV gastroenteritis. We assessed B-cell responses following intramuscular administration of a bivalent (genogroup I, genotype 1 [GI.1]/genogroup II, genotype 4 [GII.4]) VLP vaccine using protocols identical to those used to evaluate cellular immunity following experimental GI.1 HuNoV infection. The kinetics and magnitude of cellular immunity to G1.1 infection were compared to those after VLP vaccination. Intramuscular immunization with the bivalent VLP vaccine induced the production of antibody-secreting cells (ASCs) and memory B cells. ASC responses peaked at day 7 after the first dose of vaccine and returned to nearly baseline levels by day 28. Minimal increases in ASCs were seen after a second vaccine dose at day 28. Antigen-specific IgG memory B cells persisted at day 180 postvaccination for both GI.1 and GII.4 VLPs. The overall trends in B-cell responses to vaccination were similar to the trends in the responses to infection, where there was a greater bias of an ASC response toward IgA and a memory B-cell response to IgG. The magnitude of the ASC and memory B-cell responses to the GI.1 VLP component of the vaccine was also comparable to that of the responses following GI.1 infection. The production of IgG memory B cells and persistence at day 180 is a key finding and underscores the need for future studies to determine if IgG memory B cells are a correlate of protection following vaccination. (This study has been registered at ClinicalTrials.gov under registration no. NCT01168401.)

Messenger RNA vaccination and B-cell responses in NSCLC patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2573-2573 ◽  
Author(s):  
Martin Sebastian ◽  
Lotta von Boehmer ◽  
Alfred Zippelius ◽  
Frank Mayer ◽  
Martin Reck ◽  
...  
Keyword(s):  
Immune Responses ◽  
Phase I ◽  
Injection Site ◽  
B Cell ◽  
Cancer Immunotherapy ◽  
Messenger Rna ◽  
Tumor Antigens ◽  
Fold Increase ◽  
Cell Responses ◽  
B Cell Responses

2573^ Background: Vaccination with mRNA is a novel technology in cancer immunotherapy. CV9201 consists of self-adjuvanted mRNA molecules (RNActive) coding for five non small cell lung cancer (NSCLC)-associated tumor antigens (MAGE-C1, MAGE-C2, NY-ESO-1, BIRC5, 5T4). We report final results of a phase I/IIa trial of CV9201 in patients (pts.) with NSCLC. Methods: Pts. with stage IIIB/IV NSCLC with a response or stable disease after first-line chemotherapy or chemoradiation were eligible. Cohorts of 3 pts. were treated at three dose levels (400µg, 800µg and 1600µg CV9201) and observed for DLTs to select the highest tolerated dose for phase IIa. Primary endpoint was safety and tolerability; secondary endpoints were immune response, clinical efficacy and survival. Pts. received up to five vaccinations of CV9201 within 15 weeks. Antigen-specific immune responses against each of the 5 antigens were measured at baseline, and two weeks after the 3rd and 5th vaccination. Frequency of lymphocyte subsets and expression of activation and maturation markers were measured and retrospectively correlated with immunological and clinical parameters. Results: 46 pts. were included (9 phase I; 37 phase IIa); No DLTs occurred, and the 1600 µg dose was investigated in phase IIa. The most frequent related adverse events were mild to moderate injection site reactions and flu-like symptoms. 3 patients (7%) had potentially related grade 3 AEs (fatigue, injection site granuloma, asthma attack) and no related SAEs were reported. There were no objective responses. Data on PFS and survival will be presented. Antigen specific immune responses against at least one antigen were induced in 65% of pts. (39% cellular and 49% humoral). Consistently, a significant ≥2 fold increase of pre germinal center B cells (pGCB) was observed in 61% of pts. This increase of pGCB correlated significantly (p=0.0028) with increase of total CD4 effector T cells. Frequency of CD 4 T Reg cells did not increase during treatment. Conclusions: Vaccination with CV9201 has a favorable safety profile and induces T and B cell responses against all included antigens. Vaccine-induced increase of pGCB is a new finding and might be used as a biomarker in cancer immunotherapy.

scholarly journals Monkeypox-Induced Immunity and Failure of Childhood Smallpox Vaccination To Provide Complete Protection

2007 ◽  
Vol 14 (10) ◽  
pp. 1318-1327 ◽  
Author(s):  
Kevin L. Karem ◽  
Mary Reynolds ◽  
Christine Hughes ◽  
Zach Braden ◽  
Pragati Nigam ◽  
...  
Keyword(s):  
Immune Responses ◽  
B Cell ◽  
Smallpox Vaccination ◽  
Complete Protection ◽  
Recent Infection ◽  
Mild Disease ◽  
Cell Responses ◽  
B Cell Responses ◽  
Blood Specimens

ABSTRACT Following the U.S. monkeypox outbreak of 2003, blood specimens and clinical and epidemiologic data were collected from cases, defined by standard definition, and household contacts of cases to evaluate the role of preexisting (smallpox vaccine-derived) and acquired immunity in susceptibility to monkeypox disease and clinical outcomes. Orthopoxvirus-specific immunoglobulin G (IgG), IgM, CD4, CD8, and B-cell responses were measured at ∼7 to 14 weeks and 1 year postexposure. Associations between immune responses, smallpox vaccination, and epidemiologic and clinical data were assessed. Participants were categorized into four groups: (i) vaccinated cases, (ii) unvaccinated cases, (iii) vaccinated contacts, and (iv) unvaccinated contacts. Cases, regardless of vaccination status, were positive for orthopoxvirus-specific IgM, IgG, CD4, CD8, and B-cell responses. Antiorthopoxvirus immune responses consistent with infection were observed in some contacts who did not develop monkeypox. Vaccinated contacts maintained low levels of antiorthopoxvirus IgG, CD4, and B-cell responses, with most lacking IgM or CD8 responses. Preexisting immunity, assessed by high antiorthopoxvirus IgG levels and childhood smallpox vaccination, was associated (in a nonsignificant manner) with mild disease. Vaccination failed to provide complete protection against human monkeypox. Previously vaccinated monkeypox cases manifested antiorthopoxvirus IgM and changes in antiorthopoxvirus IgG, CD4, CD8, or B-cell responses as markers of recent infection. Antiorthopoxvirus IgM and CD8 responses occurred most frequently in monkeypox cases (vaccinated and unvaccinated), with IgG, CD4, and memory B-cell responses indicative of vaccine-derived immunity. Immune markers provided evidence of asymptomatic infections in some vaccinated, as well as unvaccinated, individuals.

Multiple sclerosis is associated with enhanced B cell responses to the ganglioside GD I a

1999 ◽  
Vol 5 (6) ◽  
pp. 379-388
Author(s):  
Sabrina Matá ◽  
Francesco Lolli ◽  
Mats Söderström ◽  
Francesco Pinto ◽  
Hans Link
Keyword(s):  
Multiple Sclerosis ◽  
B Cell ◽  
Neurological Diseases ◽  
Elevated Serum ◽  
Myelin Proteins ◽  
Igg Antibody ◽  
Cell Responses ◽  
Antibody Titers ◽  
B Cell Responses ◽  
Paired Serum

The occurrence and role of autoantibodies to gangliosides and other lipid-containing components of the central nervous system in Multiple Sclerosis (MS) are unsettled Using sensitive ELISAs, we measured IgG and JgM antibody titers and absorbances to the three major gangliosides GDIa, GD l b and GM, and to sulfatides, cardiolipin and myelin proteins in paired serum and cerebrospinal fluid (CSF) from patients with untreated MS, optic neuritis (ON), acute aseptic meningo-encephalitis (AM) and other neurological diseases (OND). Twenty-three per cent of 30 MS (P < 0.04) and 18% of 32 ON patient (P <0.05) presented elevated IgG antibody titers to GD) a in serum compared to 9% of patient with OND. Six (40%) of the patient with malignant MS had elevated serum IgG antibody titers to GD) a compared to one (6%) of th e patient with benign MS (P <0.04). In CSF, elevated IgG antibody titers to GDIa were measured in 13% of MS and 20% of ON patient compared to 4% of patient with OND (P < 0.03 and P < 0.02, respectively). The augmented IgG response to GD) a in serum also separated MS from Guillain-Barr6 syndrome. Compared to OND increased JgM absorbances to sulfatides and cardiolipin were observed in CSF of patient with MS, but also in AM. Elevated IgG antibody titers to myelin proteins were found more often in MS patient' serum and MS, ON and AM patient' CSF compared to OND. The data implicate that among the multitude of enhanced B-cell responses occurring in MS and ON, that directed to GD I a is common and more discriminative, and should be evaluated in future MS treatment studies.

scholarly journals Divergent Patterns of Colonization and Immune Response Elicited from Two Intestinal Lactobacillus Strains That Display Similar Properties In Vitro

2003 ◽  
Vol 71 (1) ◽  
pp. 428-436 ◽  
Author(s):  
Nabila Ibnou-Zekri ◽  
Stephanie Blum ◽  
Eduardo J. Schiffrin ◽  
Thierry von der Weid
Keyword(s):  
Immune Responses ◽  
B Cell ◽  
Immunoglobulin A ◽  
Intestinal Lumen ◽  
Probiotic Properties ◽  
Cell Responses ◽  
Specific Effects ◽  
B Cell Responses ◽  
Similar Growth

ABSTRACT Lactobacilli derived from the endogenous flora of normal donors are being increasingly used as probiotics in functional foods and as vaccine carriers. However, a variety of studies done with distinct strains of lactobacilli has suggested heterogeneous and strain-specific effects. To dissect this heterogeneity at the immunological level, we selected two strains of lactobacilli that displayed similar properties in vitro and studied their impact on mucosal and systemic B-cell responses in monoxenic mice. Germfree mice were colonized with Lactobacillus johnsonii (NCC 533) or Lactobacillus paracasei (NCC 2461). Bacterial loads were monitored for 30 days in intestinal tissues, and mucosal and systemic B-cell responses were measured. Although both Lactobacillus strains displayed similar growth, survival, and adherence properties in vitro, they colonized the intestinal lumen and translocated into mucosal lymphoid organs at different densities. L. johnsonii colonized the intestine very efficiently at high levels, whereas the number of L. paracasei decreased rapidly and it colonized at low levels. We determined whether this difference in colonization correlated with an induction of different types of immune responses. We observed that colonization with either strain induced similar germinal center formation and immunoglobulin A-bearing lymphocytes in the mucosa, suggesting that both strains were able to activate mucosal B-cell responses. However, clear differences in patterns of immunoglobulins were observed between the two strains in the mucosa and in the periphery. Therefore, despite similar in vitro probiotic properties, distinct Lactobacillus strains may colonize the gut differently and generate divergent immune responses.

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