scholarly journals Yersinia pestis Antigen F1 but Not LcrV Induced Humoral and Cellular Immune Responses in Humans Immunized with Live Plague Vaccine—Comparison of Immunoinformatic and Immunological Approaches

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 698
Author(s):  
Valentina A. Feodorova ◽  
Anna M. Lyapina ◽  
Maria A. Khizhnyakova ◽  
Sergey S. Zaitsev ◽  
Yury V. Saltykov ◽  
...  
Keyword(s):  
Immune Responses ◽  
B Cell ◽  
Yersinia Pestis ◽  
In Silico ◽  
Rational Design ◽  
Limited Information ◽  
B Cell Epitopes ◽  
Cellular Immune Responses ◽  
Cellular Immune ◽  
Plague Vaccine

The recent progress in immunoinformatics provided the basis for an accelerated development of target-specific peptide vaccines as an alternative to the traditional vaccine concept. However, there is still limited information on whether the in silico predicted immunoreactive epitopes correspond to those obtained from the actual experiments. Here, humoral and cellular immune responses to two major Yersinia pestis protective antigens, F1 and LcrV, were studied in human donors immunized with the live plague vaccine (LPV) based on the attenuated Y. pestis strain EV line NIIEG. The F1 antigen provided modest specific cellular (mixed T helper 1 (Th1)/Th2 type) and humoral immune responses in vaccinees irrespective of the amount of annual vaccinations and duration of the post-vaccination period. The probing of the F1 overlapping peptide library with the F1-positive sera revealed the presence of seven linear B cell epitopes, which were all also predicted by in silico assay. The immunoinformatics study evaluated their antigenicity, toxicity, and allergenic properties. The epitope TSQDGNNH was mostly recognized by the sera from recently vaccinated donors rather than antibodies from those immunized decades ago, suggesting the usefulness of this peptide for differentiation between recent and long-term vaccinations. The in silico analysis predicted nine linear LcrV-specific B-cell epitopes; however, weak antibody and cellular immune responses prevented their experimental evaluation, indicating that LcrV is a poor marker of successful vaccination. No specific Th17 immune response to either F1 or LcrV was detected, and there were no detectable serum levels of F1-specific immunoglobulin A (IgA) in vaccinees. Overall, the general approach validated in the LPV model could be valuable for the rational design of vaccines against other neglected and novel emerging infections with high pandemic potency.

scholarly journals Humoral and cellular immune responses to Yersinia pestis Pla antigen in humans immunized with live plague vaccine

2018 ◽  
Vol 12 (6) ◽  
pp. e0006511 ◽  
Author(s):  
Valentina A. Feodorova ◽  
Anna M. Lyapina ◽  
Maria A. Khizhnyakova ◽  
Sergey S. Zaitsev ◽  
Lidiya V. Sayapina ◽  
...  
Keyword(s):  
Immune Responses ◽  
Yersinia Pestis ◽  
Cellular Immune Responses ◽  
Cellular Immune ◽  
Plague Vaccine

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

scholarly journals Humoral and Cellular Immune Responses to Yersinia pestis Infection in Long-Term Recovered Plague Patients

2011 ◽  
Vol 19 (2) ◽  
pp. 228-234 ◽  
Author(s):  
Bei Li ◽  
Chunhong Du ◽  
Lei Zhou ◽  
Yujing Bi ◽  
Xiaoyi Wang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Yersinia Pestis ◽  
Mononuclear Cells ◽  
Vaccine Development ◽  
Effective Vaccine ◽  
Peripheral Blood Mononuclear ◽  
Content Type ◽  
Cellular Immune Responses ◽  
Significant Difference ◽  
Cellular Immune

ABSTRACTPlague is one of the most dangerous diseases and is caused byYersinia pestis. Effective vaccine development requires understanding of immune protective mechanisms against the bacterium in humans. In this study, the humoral and memory cellular immune responses in plague patients (n= 65) recovered fromY. pestisinfection during the past 16 years were investigated using a protein microarray and an enzyme-linked immunosorbent spot assay (ELISpot). The seroprevalence to the F1 antigen in all recovered patients is 78.5%. In patients infected more than a decade ago, the antibody-positive rate still remains 69.5%. There is no difference in the antibody presence between gender, age, and infected years, but it seems to be associated with the F1 antibody titers during infection (r= 0.821;P< 0.05). Except F1 antibody, the antibodies against LcrV and YopD were detected in most of the patients, suggesting they could be the potential diagnostic markers for detecting the infection of F1-negative strains. Regarding cellular immunity, the cell number producing gamma interferon (IFN-γ), stimulated by F1 and LcrV, respectively,in vitroto the peripheral blood mononuclear cells of 7 plague patients and 4 negative controls, showed no significant difference, indicating F1 and LcrV are not dominant T cell antigens against plague for a longer time in humans. Our findings have direct implications for the future design and development of effective vaccines againstY. pestisinfection and the development of new target-based diagnostics.

scholarly journals Regulatory B Cell (B10 Cell) Expansion during Listeria Infection Governs Innate and Cellular Immune Responses in Mice

2012 ◽  
Vol 190 (3) ◽  
pp. 1158-1168 ◽  
Author(s):  
Mayuka Horikawa ◽  
Eric T. Weimer ◽  
David J. DiLillo ◽  
Guglielmo M. Venturi ◽  
Rosanne Spolski ◽  
...  
Keyword(s):  
Immune Responses ◽  
B Cell ◽  
Cell Expansion ◽  
Regulatory B Cell ◽  
Cellular Immune Responses ◽  
Cellular Immune ◽  
Listeria Infection

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&lt;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 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.

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