scholarly journals Humoral and cellular immune responses to SARS CoV-2 vaccination in Persons with Multiple Sclerosis and NMOSD patients receiving immunomodulatory treatments

2021 ◽  
Author(s):  
Henry Bock ◽  
Thomas Juretzek ◽  
Robert Handreka ◽  
Johanna Ruhnau ◽  
Karl Reuner ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Response ◽  
T Cell ◽  
Immune Responses ◽  
B Cell ◽  
Humoral Immune Response ◽  
Humoral Immune ◽  
Cell Responses ◽  
Cellular Immune Responses ◽  
Cellular Immune

Abstract Background: Vaccination against SARS CoV-2 results in excellent personal protection against a severe course of COVID19. In persons with Multiple Sclerosis (PwMS) vaccination efficacy may be reduced by immunomodulatory medications. Objective: To assess the vaccination induced cellular and humoral immune response in PwMS receiving disease modifiying therapies. Methods: In a monocentric observational study on PwMS and patients with Neuromyelitis optica we quantified the cellular and humoral immune responses to SARS CoV-2. Results: PwMS receiving Glatirameracetate, Interferon-beta, Dimethylfumarate, Cladribine or Natalalizumab had intact humoral and cellular immune responses following vaccination against SARS CoV-2. B-cell depleting therapies reduced B-cell responses but did not affect T cell responses. S1P inhibitors strongly reduced humoral and cellular immune responses. There was a good agreement between the Interferon gamma release assay and the T-SPOT assay used to measure viral antigen induced T-cell responses. Conclusion: This study demonstrates that S1P inhibitors impair the cellular and humoral immune response in SARS CoV-2 vaccination, whereas patients receiving B-cell depleting therapies mount an intact cellular immune response. These data can support clinicians in counselling their PwMS and NMOSD patients during the COVID 19 pandemic.

scholarly journals Reduced schedule of human anti rabies immunization with Fuenzalida & Palacios vaccine

1989 ◽  
Vol 31 (1) ◽  
pp. 23-27 ◽  
Author(s):  
Carlos Roberto Zanetti ◽  
Silvana Regina Favoretto ◽  
Milene Silva Tino ◽  
Avelino Albas ◽  
Elizabeth Juliana G. Valentini ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Humoral Immune Response ◽  
The Other ◽  
Double Dose ◽  
Humoral Immune ◽  
Cellular Immune Responses ◽  
Lymphoblastic Transformation ◽  
Cellular Immune

The present study evaluates the humoral and cellular immune responses in 35 volunteers submited to short antirabies vaccination schedules with the Fuenzalida & Palacios vaccine based on the administration of doses on non consecutive days. The volunteers were divided into two groups. The first group received a total number of five doses given on days 0, 4, 7, 20 and 35. The other group received four doses, the first one being a double dose given on day 0 and than three other single doses on days 7, 20 and 35. The evaluation of humoral immune response was carried out by serum neutralization (SN) and indirect immunofluorescense (IIF) tests, while the cellular immune response was evaluated by lymphoblastic transformation assay (LTA) and skin test (ST). According to our results these reduced schedules elicited early and effective humoral and cellulafimmune responses to rabies antigen suggesting that new reduced schedules should be extensively studied in order to give the proper bases to the proposition of changes in the current long-term schedule.

Idiotype Vaccination of Untreated Indolent B-Cell Lymphoma: Durable Objective Remissions and Association of Superior Outcome with Cellular Immune Responses

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 235-235 ◽  
Author(s):  
Marcelo A. Navarrete ◽  
Kristina Heining-Mikesch ◽  
Cristina Bertinetti-Lapatki ◽  
Marcus Duehren-von Minden ◽  
Andrea Hafkemeyer ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune Responses ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Humoral Immune ◽  
Cellular Immune Responses ◽  
Humoral Immune Responses ◽  
Cellular Immune

Abstract Idiotype vaccination refers to active immunization of B-cell lymphoma (B-NHL) patients with the clonal immunoglobulin (Ig) expressed by the tumor cells. After systemic cytoreductive therapy, idiotype vaccination has been shown to induce specific cellular and humoral immune responses; and humoral responses in particular are associated with prolonged remission and encouraging survival rates. Conventional idiotype vaccines are composed of the entire lymphoma-derived Ig coupled to the immunogenic carrier KLH and are administered subcutaneously with adjuvant. We have developed a idiotype production strategy based on bacterial expression of the lymphoma-derived idiotype as a recombinant Fab fragment (Bertinetti et al., EJH 2006). Intradermal administration of this antigen with lipid-based adjuvant and subcutaneous coadministration of GM-CSF had excellent immunogenicity in a phase I trial of advanced, heavily pretreated B-NHL patients (Bertinetti et al., Cancer Research 2006). In a subsequent phase II trial, 20 patients with untreated indolent B-NHL (14 follicular [FL], 3 nodal marginal zone [nMZL], 3 mantle cell [MCL]) and without immediate need for cytoreduction received at least 6 monthly idiotype vaccinations. No grade IV toxicities were seen, and the sole case of grade III toxicity, generalized erythema, did not preclude completion of the vaccination schedule. Prior to vaccination, 5/19 patients (26%) had decreased CD4+ and 6/19 patients (31%) low CD8+ T cells counts. Furthermore, 10/12 anti-HbS-negative patients (83%) failed to mount a detectable immune response to a conventional hepatitis B vaccine administered concomitantly to idiotype vaccination. Despite this functional immunodeficiency, 12/18 analyzed patients (66%) developed a cellular immune response to idiotype as detected by enumeration of IFNgamma-secreting cells by DC-ELISpot. The ELISpot protocol was validated by blinded interlaboratory testing (www.cimt.de). The frequency of idiotype-responding T cells increased from the 2nd to the 6th vaccination and could be effectively boostered by maintenance immunization in 3-monthly intervals. In vitro stimulation of PBMC from responding patients with idiotype induced specific proliferation of CD4+ T-cells and a shift towards a Th1 response in post-vaccination samples. In addition, 8/18 analyzed patients (44%) developed anti-idiotype IgG or IgM antibodies as assessed by ELISA, and the combined immune response rate was 85%. After a median follow-up of 34 months, 8 patients (40%) are progression-free, and 10 (50%) did not require cytoreductive therapy. Cellular immune responses were associated with superior PFS (p<0.05), and 5 of 6 non-responders eventually required cytoreductive therapy. Humoral immune responses were not related to PFS. Six patients (30%; only FL or nMZL) achieved an objective partial remission, including near-complete disappearance of a large submandibular mass and one subcutaneous lymphoma mass. All objective responders developed specific cellular immunity, but only 4 anti-idiotype antibodies. Five patients are in continuing remission for 12–49 months. Intradermal immunization with the chosen idiotype formulation has excellent immunogenicity despite a severely impaired immune function in untreated B-NHL patients. Furthermore, this is the first active immunotherapy trial showing objective and durable lymphoma responses in first-line therapy at a higher rate than expected for spontaneous remissions. In this setting, and in contrast to conventional idiotype vaccination schedules, cellular anti-idiotype immunity may play a crucial role for a favorable clinical outcome. Since passive humoral anti-lymphoma immunity can be easily transferred by infusions of commercially available monoclonal antibodies, synergistic benefit may be envisioned for an initial vaccination course aimed to prime anti-idiotype T-cells combined with subsequent passive immunotherapy.

scholarly journals Baseline Levels of Influenza-Specific B Cells and T Cell Responses Modulate Human Immune Responses to Swine Variant Influenza A/H3N2 Vaccine

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 126
Author(s):  
Lilin Lai ◽  
Nadine Rouphael ◽  
Yongxian Xu ◽  
Amy C. Sherman ◽  
Srilatha Edupuganti ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Influenza A ◽  
Vaccine Dose ◽  
T Cell Responses ◽  
Post Vaccination ◽  
Cell Responses ◽  
Cellular Immune Responses ◽  
Cellular Immune

The cellular immune responses elicited by an investigational vaccine against an emergent variant of influenza (H3N2v) are not fully understood. Twenty-five subjects, enrolled in an investigational influenza A/H3N2v vaccine study, who received two doses of vaccine 21 days apart, were included in a sub-study of cellular immune responses. H3N2v-specific plasmablasts were determined by ELISpot 8 days after each vaccine dose and H3N2v specific CD4+ T cells were quantified by intracellular cytokine and CD154 (CD40 ligand) staining before vaccination, 8 and 21 days after each vaccine dose. Results: 95% (19/20) and 96% (24/25) subjects had pre-existing H3N2v specific memory B, and T cell responses, respectively. Plasmablast responses at Day 8 after the first vaccine administration were detected against contemporary H3N2 strains and correlated with hemagglutination inhibition HAI (IgG: p = 0.018; IgA: p < 0.001) and Neut (IgG: p = 0.038; IgA: p = 0.021) titers and with memory B cell frequency at baseline (IgA: r = 0.76, p < 0.001; IgG: r = 0.74, p = 0.0001). The CD4+ T cells at Days 8 and 21 expanded after prime vaccination and this expansion correlated strongly with early post-vaccination HAI and Neut titers (p ≤ 0.002). In an adult population, the rapid serological response observed after initial H3N2v vaccination correlates with post-vaccination plasmablasts and CD4+ T cell responses.

B Cell-Related Chemokine (CXCL13) in CSF is Correlated with the Intrathecal Humoral Immune Response in Patients with Multiple Sclerosis

2020 ◽  
Vol 37 ◽  
pp. 101569
Author(s):  
Sawsan Feki ◽  
Mariem Dammak ◽  
Sabrina Mejdoub ◽  
Saba Gargouri ◽  
Salma Sakka ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Response ◽  
B Cell ◽  
Humoral Immune Response ◽  
Humoral Immune

scholarly journals Monitoring CD8 T cell responses to NY-ESO-1: Correlation of humoral and cellular immune responses

2000 ◽  
Vol 97 (9) ◽  
pp. 4760-4765 ◽  
Author(s):  
E. Jager ◽  
Y. Nagata ◽  
S. Gnjatic ◽  
H. Wada ◽  
E. Stockert ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Responses ◽  
Cellular Immune Responses ◽  
Cellular Immune

scholarly journals Preserved T-cell Response in anti-CD20 Treated Multiple Sclerosis Patients Following SARS-CoV-2 Vaccination

2021 ◽  
Author(s):  
Simon Faissner ◽  
Neele Heitmann ◽  
Ricarda Rohling ◽  
Ulas Ceylan ◽  
Marielena Bongert ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Response ◽  
T Cell ◽  
B Cell ◽  
T Cell Response ◽  
Th2 Cells ◽  
Multiple Sclerosis Patients ◽  
Cellular Immune ◽  
Cell Repopulation

Abstract The SARS-CoV-2 pandemic has tremendous implications for the management of patients with autoimmune conditions such as multiple sclerosis (MS) under immune therapies targeting CD20+ B cells (aCD20). We here investigated humoral and cellular immune responses, including neutralization against SARS-CoV-2 WT and delta variant and T cell responses of aCD20-treated MS patients following SARS-CoV-2 vaccination compared to healthy controls. aCD20-treated MS patients had lower anti-SARS-CoV-2-Spike titers, which correlated with B-cell repopulation. Sera of aCD20 treated patients had reduced capacity to neutralize WT and delta pseudoviruses in vitro. On the contrary, aCD20 treated patients elicited higher frequencies of CD3+ T cells, Th1 cells, Th2 cells, Tc1 cells and CD8+IFN-γ+IL-2+ cells. In summary, aCD20 treated patients have a reduced humoral immune response, depending on B cell repopulation, in accordance with a shift of cellular immune response to a stronger Th1, Th2 and Tc1 phenotype, suggesting strong cellular protection against SARS-CoV-2.

scholarly journals Association between Reactogenicity and Immunogenicity after Vaccination with BNT162b2

Vaccines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1089
Author(s):  
Stilla Bauernfeind ◽  
Bernd Salzberger ◽  
Florian Hitzenbichler ◽  
Karolina Scigala ◽  
Sebastian Einhauser ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Immune Responses ◽  
Humoral Immune Response ◽  
Adverse Reactions ◽  
Medical Center ◽  
Neutralization Activity ◽  
Humoral Immune ◽  
Cell Mediated Immune Response ◽  
Severe Adverse Reactions

It is not clear whether there is an association between adverse reactions and immune response after vaccination. Seven hundred and thirty-five vaccinees from our University Medical Center vaccination clinic provided information about sex, age and adverse reactions after first and second vaccination with BNT162b2. Adverse reactions were categorized into three groups: no or minor on the injection side, moderate (not further classified) and severe—defined as any symptom(s) resulting in sick leave. We chose 38 vaccinees with the most severe adverse reactions and compared their humoral and T-cell-mediated immune responses after second vaccination with those of 38 sex and age matched controls without or only minor injection-side related adverse reactions. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-receptor binding domain (RBD) IgG titers were detectable in all participants (median 5528; range 958–26,285). Men with severe adverse reactions had 1.5-fold higher median SARS-CoV-2 RBD IgG titers compared to men without adverse reactions (median 7406 versus 4793; p < 0.001). Similarly; neutralization activity was significantly higher in men with severe adverse reactions (half maximal inhibitory concentrations (IC50) median 769 versus 485; p < 0.001). Reactogenicity did not influence humoral immune response in women nor T-cell-mediated immune response in any sex. To conclude; adverse reactions after vaccination with BNT162b2 do influence humoral immune response yet only in men and are not a prerequisite for a robust antibody response.

scholarly journals A Soluble Version of Nipah Virus Glycoprotein G Delivered by Vaccinia Virus MVA Activates Specific CD8 and CD4 T Cells in Mice

Viruses ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 26 ◽  
Author(s):  
Georgia Kalodimou ◽  
Svenja Veit ◽  
Sylvia Jany ◽  
Ulrich Kalinke ◽  
Christopher C. Broder ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Vaccinia Virus ◽  
G Protein ◽  
Nipah Virus ◽  
Cell Responses ◽  
Cellular Immune Responses ◽  
Glycoprotein G ◽  
Cellular Immune

Nipah virus (NiV) is an emerging zoonotic virus that is transmitted by bats to humans and to pigs, causing severe respiratory disease and often fatal encephalitis. Antibodies directed against the NiV-glycoprotein (G) protein are known to play a major role in clearing NiV infection and in providing vaccine-induced protective immunity. More recently, T cells have been also shown to be involved in recovery from NiV infection. So far, relatively little is known about the role of T cell responses and the antigenic targets of NiV-G that are recognized by CD8 T cells. In this study, NiV-G protein served as the target immunogen to activate NiV-specific cellular immune responses. Modified Vaccinia virus Ankara (MVA), a safety-tested strain of vaccinia virus for preclinical and clinical vaccine research, was used for the generation of MVA–NiV-G candidate vaccines expressing different versions of recombinant NiV-G. Overlapping peptides covering the entire NiV-G protein were used to identify major histocompatibility complex class I/II-restricted T cell responses in type I interferon receptor-deficient (IFNAR−/−) mice after vaccination with the MVA–NiV-G candidate vaccines. We have identified an H2-b-restricted nonamer peptide epitope with CD8 T cell antigenicity and a H2-b 15mer with CD4 T cell antigenicity in the NiV-G protein. The identification of this epitope and the availability of the MVA–NiV-G candidate vaccines will help to evaluate NiV-G-specific immune responses and the potential immune correlates of vaccine-mediated protection in the appropriate murine models of NiV-G infection. Of note, a soluble version of NiV-G was advantageous in activating NiV-G-specific cellular immune responses using these peptides.

scholarly journals Impaired Cellular Immune Responses During the First Week of Severe Acute Influenza Infection

2020 ◽  
Vol 222 (7) ◽  
pp. 1235-1244 ◽  
Author(s):  
Jackson S Turner ◽  
Tingting Lei ◽  
Aaron J Schmitz ◽  
Aaron Day ◽  
José Alberto Choreño-Parra ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
T Cell ◽  
Immune Responses ◽  
Influenza Infection ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Cell Responses ◽  
Cellular Immune Responses ◽  
Inflammatory Monocytes ◽  
Cellular Immune

Abstract Background Cellular immune responses are not well characterized during the initial days of acute symptomatic influenza infection. Methods We developed a prospective cohort of human subjects with confirmed influenza illness of varying severity who presented within a week after symptom onset. We characterized lymphocyte and monocyte populations as well as antigen-specific CD8+ T-cell and B-cell responses from peripheral blood mononuclear cells using flow cytometry and enzyme-linked immunospot assays. Results We recruited 68 influenza-infected individuals on average 3.5 days after the onset of symptoms. Three patients required mechanical ventilation. Influenza-specific CD8+ T-cell responses expanded before the appearance of plasmablast B cells. However, the influenza-specific CD8+ T-cell response was lower in infected subjects than responses seen in uninfected control subjects. Circulating populations of inflammatory monocytes were increased in most subjects compared with healthy controls. Inflammatory monocytes were significantly reduced in the 3 subjects requiring mechanical ventilation. Inflammatory monocytes were also reduced in a separate validation cohort of mechanically ventilated patients. Conclusions Antigen-specific CD8+ T cells respond early during acute influenza infection at magnitudes that are lower than responses seen in uninfected individuals. Circulating inflammatory monocytes increase during acute illness and low absolute numbers are associated with very severe disease.

Characterization of Cellular Immune Responses to a Recombinant Idiotype Vaccine by ELISPOT and Identification of MHC Class I-Restricted T Cell Epitopes by Peptide Mapping.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1409-1409 ◽  
Author(s):  
Cristina M. Bertinetti ◽  
Hendrik Veelken
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
B Cell ◽  
Mhc Class I ◽  
B Cell Lymphoma ◽  
Class I ◽  
Fab Fragment ◽  
Cellular Immune Responses ◽  
Idiotype Vaccine ◽  
Cellular Immune

Abstract Induction of tumor-specific immune responses by idiotype vaccination is a promising strategy for biological therapy of indolent B cell lymphomas. In a previous report, we have described immune responses in a subset of patients participating in a phase I clinical trial primarily designed to demonstrate safety and efficacy of a recombinant idiotype vaccine (Veelken et al., ASH abstract #3342, 2003). In this trial, B-NHL patients who had relapsed after standard chemotherapy received repetitive intradermal vaccinations with recombinant idiotype Fab fragment derived from their tumor mixed with lipid-based adjuvant and concurrent subcutaneous GM-CSF at the same site. We now present the final analysis of cellular immune responses in this cohort. Peripheral blood lymphocytes (PBL) were obtained prior to and on various time points during and after vaccinations. Cryopreserved PBL were stimulated twice by autologous dendritic cells (DC) exposed to the autologous Fab protein for cross-presentation as MHC class I-bound peptides. INFγ-secreting cells were subsequently quantified by ELISPOT with Fab-presenting DC. Alternatively, freshly thawed PBL were directly assayed with recombinant Fab by ELISPOT without prestimulation. An increase in the frequency of Fab-responding PBL was detected in 7 of 15 evaluable patients with the prestimulation assay and in 4 of 10 patients by direct quantitation, resulting in a combined cellular response rate of 53% (9 of 17). A cellular immune response showed a trend for correlation with extended progression-free survival (p=0.08). T cell responses were predominantly idiotype-specific since lesser or no increases in IFNγ-secreting cells were detected against light chain- and VH family-matched control Fabs. Interestingly, a much higher base-line reactivity was observed against the control Fabs in comparison to the patient’s lymphoma Fab in four patients, pointing to the possibility of tumor-specific anergy in lymphoma patients that can at least be partially corrected by active immunization. In an effort to identify the MHC class I-presented idiotype-derived peptides, potential binding motifs were defined by reverse immunology with the SYFPEITHI algorithm (www.syfpeithi.de). Ten candidate peptides from the variable and constant region of an immune responder’s idiotype heavy chain were synthesized and evaluated with post-vaccination PBL by ELISPOT without prestimulation. A peptide derived from the CDR2 region showed a significantly higher response compared to an unrelated peptide control (p=0.0013). Additional peptides derived from the FWR1, CDR1, and CDR2 also showed a significant stimulation, but only in comparison to a no peptide control. ELISPOT offers a valuable tool to monitor cellular immune reponses and demonstrates successful induction of tumor immunity in pretreated, tumor bearing and immunosuppressed B cell lymphoma patients. Supported by Deutsche Krebshilfe

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