Lack of Response to Vaccination in MGUS and Stable Myeloma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1852-1852 ◽  
Author(s):  
Rao H Prabhala ◽  
Yvonne A Efebera ◽  
Saem Lee ◽  
Andrew J Han ◽  
Dheeraj Pelluru ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Immune Response ◽  
T Cell ◽  
Immune Responses ◽  
Antibody Response ◽  
Surface Antigen ◽  
Research Funding ◽  
Base Line ◽  
Cellular Immune Responses ◽  
Cellular Immune

Abstract Abstract 1852 Poster Board I-878 Multiple myeloma patients suffer from infection related complications. Abnormalities in both cellular and humoral immune responses have been considered responsible. Patients have been routinely immunized with vaccinations to prevent infection related problems, however, efficacy of such vaccination in early or stable myeloma remains unclear. Previously, we have shown immunomodulatory and T cell co-stimulatory effects of lenalidomide, which can up-regulate cellular immune responses in myeloma. Based on these results we initiated a study to evaluate the efficacy of lenalidomide compared to placebo on the effect of Hepatitis B (HepB) vaccination in patients with monoclonal gamopathy of undetermined significance (MGUS), smoldering myeloma or stable multiple myeloma (MM) not requiring any therapy. Patients were randomized to lenalidomide or placebo for 14 days with HepB vaccination on day 8. They were given option for 2nd and 3rd HepB vaccinations at 1 month and 6 month. Primary objective was to evaluate antibody response to Hepatitis Surface antigen (HepBSAg) at 1 month after vaccination. We also measured HepBSAg-specific cellular immune responses using HepBSAg protein and HLA-A2 peptide. At the time of data analysis, the study remains blinded. Thirty two patients have completed their initial vaccination (25 MGUS and 7 MM), while 22 patients (16 MGUS, 6 MM) have completed 3 vaccinations with 6 months follow up. None of the 32 patients, with MGUS or MM, had antibody response to vaccination at 1 month; while after 3 vaccination only 30% patients (7 of 24) demonstrated antibody response to HepBSAg (titer values 128.4±36.4). This is significantly below responses reported in literature in healthy individuals (90%). Responses in patients with MGUS (4 of 16) were not significantly different than in patients with MM (3 of 6). No base line patient characteristics predicts responders vs. non-responders. We have further analyzed HepBSAg-specific T cell immune response by detecting the presence of pentamer-positive CD8 cells with HepB surface antigen-peptide in HLA-A2+ samples. Five of seven responders were HLA-A2 positive, and none of them showed T cell response to HbSAg following vaccination as detected by change in pentamer positive cells. Three patients showed T cell-proliferative responses to HepBsAg; one of which had long term response. None of the non-responders tested demonstrated proliferative response to HepBSAg. The randomization remains blinded at the moment and hence effect of lenalidomide on immune response is not available at the present time. These results have very high clinical significance. It suggests that even in MGUS there is significant and profound functional immune suppression. Strategies to prevent infection and improve immune responses needs to be developed for both preventative purposes as well as for anti-MM vaccinations. Disclosures: Laubach: Novartis: . Richardson:Keryx Biopharmaceuticals: Honoraria. Anderson:Millenium: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding.

Hepatic Tolerance Induction Prevents Inflammatory Responses To Factor IX Expressing Cells at Supplementary Sites of Gene Transfer.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3185-3185
Author(s):  
E. Dobrzynski ◽  
F. Mingozzi ◽  
L. Wang ◽  
B. Mingle ◽  
O. Cao ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Gene Transfer ◽  
Immune Responses ◽  
Tolerance Induction ◽  
Cd8 T Cell ◽  
Factor Ix ◽  
Cell Infiltrate ◽  
Cellular Immune Responses ◽  
Cellular Immune

Abstract The use of gene replacement therapy is an attractive approach for the treatment of the genetic bleeding disorder hemophilia B (caused by mutations in the coagulation factor IX, FIX, gene). A major concern with this type of procedure is the potential for a host immune response to the therapeutic gene product, which would render treatment ineffective. Previously, we observed inflammatory, cytotoxic T lymphocyte, and antibody responses to a human FIX (hFIX) transgene product after intramuscular (IM) delivery via an E1/E3-deleted adenoviral vector (Ad-hFIX) in C57BL/6 mice. Different from this Th1-biased immune response, IM injection of adeno-associated viral (AAV) vector, a Th2-biased, non-inflammatory response led to antibody-mediated neutralization of hFIX expression, without CTL activation. In contrast to these observations on muscle-directed vector administration, hepatic AAV-hFIX gene transfer induced immune tolerance to the transgene product (JCI 111:1347). Lack of anti-hFIX formation was demonstrated even after challenge with hFIX in adjuvant. In order to examine the effect of tolerance induction on CD8+ T cell-mediated cellular immune responses, we performed the following experiments. C57BL/6 mice (n=4 per experimental group) received IM injections of AAV-hFIX vector (serotype 1) in one hind limb and/or Ad-hFIX vector in the contra-lateral leg. In the latter case, inflammation (as determined by H&E histological evaluation), CD8+ T cell infiltrate and destruction of hFIX expressing muscle fibers were obvious in both legs because of the Ad-hFIX mediated activation of CTL to hFIX. CD8+ T cell responses were strongest in Ad-hFIX transduced muscle at day 14 and in the AAV-hFIX leg at day 30. Expression of hFIX as determined by immunohistochemistry became undetectable in Ad-hFIX injected muscle by day 30, but was not completely eliminated in AAV-hFIX transduced muscle. Injection of AAV-hFIX only, did not cause inflammation of muscle tissue or CD8+ cell infiltrate. When the identical experiment was carried out in C57BL/6 mice that were expressing hFIX from hepatic gene transfer via the AAV serotype 2 vector (performed 6 weeks earlier), a substantial increase in systemic hFIX expression was observed after IM administration of the Ad and AAV-1 vectors (again injected into contra-lateral legs). However, a portion of the increased expression was subsequently lost, which correlated with inflammation and CD8+ T cell infiltrate of the Ad-hFIX transduced muscle. Interestingly, no (3/4 mice) or only minor (1/4 mice) infiltrate was observed in AAV-hFIX injected muscles. Consequently, hFIX expression persisted in the AAV, but not the Ad transduced legs. Presumably, CTL responses to adenoviral antigens were sufficient to target Ad-hFIX transduced muscle despite tolerance to the transgene product. In contrast to control mice, hepatic tolerized animals failed to form anti-hFIX after challenge by IM injection of these viral vectors. Moreover, inflammatory and destructive cellular immune responses to the transgene product were successfully prevented by hepatic tolerance induction, indicating that tolerance induced by gene transfer to the liver affects cellular as well as antibody-mediated responses and extents to tissues other than liver.

scholarly journals Effect of Bruton Tyrosine Kinase Inhibitor on Serologic and Cellular Immune Responses to Recombinant Zoster Vaccine

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1556-1556
Author(s):  
Christopher Pleyer ◽  
Kerry J Laing ◽  
Mir Ali ◽  
Christopher L McClurkan ◽  
Susan Soto ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune Responses ◽  
Injection Site ◽  
Cellular Immune Response ◽  
Research Funding ◽  
Vaccine Response ◽  
Cellular Immune Responses ◽  
Serologic Response ◽  
Cellular Immune

Abstract Introduction The recombinant zoster vaccine (RZV) is effective in preventing herpes zoster reactivation in the general population. We previously showed that patients with chronic lymphocytic leukemia (CLL), particularly those receiving Bruton tyrosine kinase inhibitors (BTKis), have decreased humoral immune responses following vaccination. The impact of vaccination on cellular immune responses in CLL patients is not well characterized. Understanding the effect of humoral and cellular immunity in CLL patients who are treatment naïve or receiving BTKis can inform vaccination strategies in this immunosuppressed patient population. Methods In this phase II open-label study (NCT03702231), patients with CLL who were either treatment naïve (TN) or receiving a BTKi (ibrutinib or acalabrutinib) received 2 doses of RZV via intramuscular injection at baseline and 3 months. Subjects were followed for 6 months and assessed for serologic response at 3 and 6 months. Serologic response was defined as a ≥ four-fold rise in anti-glycoprotein E (anti-gE) IgG serum titer at the 6 month timepoint. Cellular immune response was assessed by intracellular cytokine staining and flow cytometric analysis of gE-specific CD4+ T cells expressing upregulation of ≥2 effector molecules (interferon-γ, interleukin-2, tumor necrosis factor-α, and/or CD40 ligand). Cellular response was defined as ≥ two-fold rise over baseline and ≥320 net gE-specific CD4(2+) cells per million CD4+ T cells. Descriptive statistics were used to report vaccine response rates. Mann-Whitney test and Fisher's exact test were used to compare titers and response rates between different groups. Spearman r was used to measure the correlation between vaccine responses and clinical characteristics. All subjects completed an adverse event (AE) diary documenting any local (injection site) or systemic AE that started within 7 days after receiving the first and second vaccine dose. Results 106 subjects had serologic response assessment at 6 months. Baseline characteristics are shown in Table 1. The serologic response rate to RZV was significantly higher in the TN cohort (76.8%, 95% CI, 64.2-85.9; n = 56) compared to patients receiving a BTKi (40.0%, 95% CI,27.6-53.8; n = 50; P = .0002). Cellular vaccine response was assessed in 94 subjects at 6 months. Similarly, the rate of cellular immunity was significantly higher in the TN cohort (69.4%, 95% CI,55.5-80.5; n = 49) compared to patients treated with a BTKi (40.0%, 95% CI,27.0-54.5; n = 45, P = .0067). Paired serologic and cellular responses were available in 93 subjects. 68.5% (95% CI,55.3-79.3; n = 54) of subjects with a serologic response also had a positive cellular immune response, whereas 35.9% (95% CI,22.7-51.6; n = 39) of subjects attained a cellular immune response in absence of a serologic response (P = .0029) (Figure 1). Among subjects with a negative serologic response and a positive cellular immune response, 42.9% were TN (n = 6) and 57.1% (n = 8) received a BTKi. There was no difference in serologic or cellular responses between patients treated with ibrutinib and acalabrutinib (P > 0.05). Serologic antibody titers and T cell responder frequencies were weakly positively correlated (r = 0.26; 95%CI .05-.44; P = .0127). Serologic titers and T cell responses were not correlated with age, beta-2 microglobulin, absolute lymphocyte count, absolute peripheral blood CD19+, CD3+, CD4+ or CD8+ counts or serum immunoglobulin levels (IgA, IgG, IgM) (all P > 0.05). The most frequent local and systemic AEs were injection site pain (98.3%), injection site reaction (97.4%), headache (51.7%), and generalized myalgias (51.7%). Most AEs were grade 1-2 and all AEs resolved or returned to baseline within 7 days of vaccine administration. Conclusions RZV is safe in CLL patients and can induce both humoral and cellular immune responses. BTKi treatment was associated with impaired serologic and cellular vaccine responses compared to TN patients. Although BTKi therapy may inherently decrease vaccine immunogenicity, TN CLL patients could be more immunocompetent because of less advanced disease, thereby permitting more effective immune responses. The majority of patients with a positive antibody response also developed virus-specific T cells following vaccination. Approximately one third of patients without a positive serologic response developed virus reactive T cells. Figure 1 Figure 1. Disclosures Laing: Curevo Vaccine: Consultancy; MaxHealth LLC: Consultancy. Wiestner: Acerta Pharma: Research Funding; Pharmacyclics LLC: Research Funding; Merck: Research Funding; Nurix: Research Funding; Verastem: Research Funding; Genmab: Research Funding. Koelle: Merck: Research Funding; Curevo Vaccine: Other: Scientific Advisory Board ; MaxHealth LLC: Other: Scientific Advisory Board ; Oxford Immunotec: Research Funding; Sensei Biotherapeutics: Research Funding; Sanofi Pasteur: Research Funding. Sun: Genmab: Research Funding.

scholarly journals Characterization of the Early Humoral and Cellular Response Developed in Oncohematological Patients Post-Vaccination with One Dose Against COVID-19

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 195-195
Author(s):  
Magdalena Corona De Lapuerta ◽  
Sara Rodriguez-Mora ◽  
Guiomar Casado-Fernandez ◽  
Javier Garcia-Pérez ◽  
Lorena Vigon ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune Responses ◽  
Research Funding ◽  
Similar Response ◽  
Cellular Cytotoxicity ◽  
Hematopoietic Stem ◽  
Cellular Immune Responses ◽  
Healthy Donors ◽  
Cellular Immune

Abstract Background: Oncohematological patients present a variable immune response against many vaccines, due to the immunodeficiency caused by the disease and its treatment. The experience of vaccination against COVID-19 in oncohematological patients is low and mostly limited to studies of humoral immunity. However, the humoral and cellular immune responses between different oncohematological diseases (OHD) have not been compared. Objective: To compare the humoral and cellular immune responses in four groups of patients with OHD after receiving the first dose of one COVID-19 vaccine. Materials & methods: We recruited 53 patients in four groups according to diagnosis: Chronic Lymphatic Leukemia (CLL) (n=14), Chronic Myeloid Leukemia (CML) (n=11), Multiple Myeloma (MM) (n=15), and Allogeneic Hematopoietic Stem Cell Transplantation (ASCT) (n=13) (Table 1). Samples were collected prior to vaccination and 3 weeks after receiving one dose of COMIRNATY (BioNTech-Pzifer), mRNA-1273 (Moderna), or AZD1222 (AstraZeneca). Twenty-six healthy donors with similar vaccination pattern were recruited. IgG titers against SARS-CoV-2 were quantified by Euroimmun-Anti-SARS-CoV-2 ELISA. Direct cellular cytotoxicity (DCC) was determined against Vero E6 cells infected with pseudotyped SARS-CoV-2, measuring caspase-3 activation after co-culture with PBMCs, in which cytotoxic populations were phenotyped by flow cytometry. Antibody-dependent cellular cytotoxicity (ADCC) analyses were performed using Annexin V on Raji cells as a target. Results: 1) Early humoral response against COVID-19 vaccination in patients with CML was 5.1- (p<0.0001), 2.8- (p=0.0027), and 3.2-fold (p<0.0001) higher than in patients with CLL, MM and HSCT, respectively, and 3.5-fold higher than in healthy donors (p=0.0460) (Fig. 1). 84% of CLL patients did not develop detectable IgG titers. Individuals with OHD developed lower titres of neutralizing antibodies than healthy donors. 2) Unspecific ADCC was overall reduced in patients with OHD, mostly in individuals with ASCT (3.2-fold lower (p<0,0001)), whereas ADCC was reduced 2.2- (p<0.0001), 1.8- (p=0.0040), and 2.2-fold (p<0.0001) in individuals with CLL, CML and MM, respectively (Fig. 2A). However, specific DCC was increased 4.7-, 8.1- (p=0.0189), and 2.1-fold, respectively, in PBMCs from patients with CLL, MM, or ASCT, in comparison with healthy donors, whereas patients with CML showed a very similar response than healthy donors (Fig. 2B). 3) Levels of CD3+CD8+TCRγδ+ T cells were increased 2.2-, 2.1-, 2.7-, and 4.3-fold (p=0.0394) in patients with CLL, CML, MM, and ASCT, respectively, in comparison with healthy donors. CD3+CD8-TCRγδ+ T cells were also increased in patients with OHD, expressing high levels of the degranulation marker CD107a. However, the levels of CD3-CD56+CD107a+ NK cells were reduced 4.2- (p=0.0003) and 3.6-fold (p=0.0010) in PBMCs from patients with MM and ASCT, respectively, in comparison with healthy donors. Conclusions: We found significant differences in the early humoral immune response after one single dose of COVID-19 vaccine depending on the OHD analyzed. It was observed for the first time that the early cytotoxic immune response is efficient in all groups of patients, although superior in those who were not exposed to ASCT. Most cytotoxic activity relied on CD8+ T cells. These data can be useful to determine the efficacy of COVID-19 vaccines in patients with OHD. Figure 1 Figure 1. Disclosures Garcia Gutierrez: BMS: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding.

CT7 (MAGE-C1)-Specific Cellular Immune Responses in the Bone Marrow Microenvironment of Multiple Myeloma Patients.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 356-356
Author(s):  
Hearn J. Cho ◽  
Len Farol ◽  
Jonathan T. Truong ◽  
Wayne R. Austin ◽  
Yao-Tseng Chen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
T Cell ◽  
Immune Responses ◽  
Positive Control ◽  
Type I ◽  
Myeloma Patient ◽  
Myeloma Cells ◽  
Cellular Immune Responses ◽  
Cellular Immune

Abstract In previous studies we demonstrated that CT7 (MAGE-C1), a member of the type I MAGE family of Cancer-Testis antigens, was expressed in 82% of primary multiple myeloma specimens. Higher percentages of CT7-expressing cells were correlated with abnormally elevated plasma cell proliferation in these patients, and CT7 was co-expressed in proliferating myeloma cells. Therefore, a tumor vaccine targeting CT7 may preferentially eliminate proliferating myeloma cells, resulting in long-term cures. The type I MAGE were originally identified because they elicited cellular immune responses in melanoma patients whose tumors expressed these antigens. These data suggest the hypothesis that CT7 expression in myeloma cells may similarly elicit T cell immunity in myeloma patients. To test this hypothesis, we examined lymphocytes from myeloma patient bone marrow, the tumor microenvironment. Lymphocytes were isolated from myeloma patient bone marrow aspirates by magnetic bead depletion of CD138 plasma cells followed by plating to remove adherent monocyte. Bone marrow lymphocytes were then expanded by two rounds of stimulation with anti-CD3, anti-CD28 monoclonal antibody (mAb)-conjugated beads and 50 IU/ml recombinant human (rhu) IL-2. Autologous myeloid dendritic cells (mDC) served as antigen-presenting cells for this analysis; they were prepared from peripheral blood monocytes by cultivation with rhu-IL-4 and GM-CSF, then matured with a cytokine cocktail consisting of TNFα , rhu-IL-1β , rhu IL-6, and prostaglandin E2. Myeloid DC were then transduced with in vitro transcribed CT7 mRNA or positive control antigen flu matrix protein (MP) mRNA by electroporation. Negative control mDC were also mock electroporated without mRNA. The dendritic cells were then co-cultured with the expanded bone marrow lymphocytes at 1:1 and 1:20 ratios in IFNγ ELISpot assays. Positive control stimulation with the T cell superantigen Staphylococcal enterotoxin B (SEB) served to assess overall responsiveness of the polyclonal lymphocyte population. Results from four patients are shown in Table 1. Two of four patients, both diagnosed with stage IIIa disease and both expressing CT7 mRNA by RT-PCR, exhibited increases in IFNγ-secreting lymphocytes when co-incubated with CT7-transduced mDC compared to mock electroporated mDC. In contrast, one stage I patient who did not express CT7 mRNA and one stage IIIb, CT7+ patient did not show any increase in IFNγ-secreting cells in response to CT7-transduced mDC stimulation. These data indicated that CT7 expression in myeloma cells can provoke cellular immunity, and suggests that CT7-specific vaccines may boost this immunity. These ongoing studies will also characterize the antigenic T cell epitopes of CT7. Table 1. CT7-specific bone marrow lymphocytes Patient Stage CT7 mRNA expression Mock CT7 Flu MP SEB IFNγ-secreting cells/50,000 bone marrow lymphocytes 1 IIIa + 28.0 ± 7.1 57.7 ± 5.9 nd 288 ± 42.1 2 IIIa + 6.3 ± 2.3 27.7 ± 10.1 17.7 ± 5.3 90.0 ± 50.3 3 Ia − 6.0 ± 1.0 8.5 ± 0.5 nd 91.5 ± 54.5 4 IIIb + 1.5 ± 0.5 4.5 ± 0.5 nd 72.0 ± 43.0

scholarly journals Induction of Specific Immune Responses by Severe Acute Respiratory Syndrome Coronavirus Spike DNA Vaccine with or without Interleukin-2 Immunization Using Different Vaccination Routes in Mice

2007 ◽  
Vol 14 (7) ◽  
pp. 894-901 ◽  
Author(s):  
Hui Hu ◽  
Xinya Lu ◽  
Ling Tao ◽  
Bingke Bai ◽  
Zhenfeng Zhang ◽  
...  
Keyword(s):  
T Cell ◽  
Severe Acute Respiratory Syndrome ◽  
Immune Responses ◽  
Antibody Response ◽  
Dna Vaccine ◽  
Cell Response ◽  
Interleukin 2 ◽  
T Cell Response ◽  
Cellular Immune Responses ◽  
Cellular Immune

ABSTRACT DNA vaccines induce humoral and cellular immune responses in animal models and humans. To analyze the immunogenicity of the severe acute respiratory syndrome (SARS) coronavirus (CoV), SARS-CoV, spike DNA vaccine and the immunoregulatory activity of interleukin-2 (IL-2), DNA vaccine plasmids pcDNA-S and pcDNA-IL-2 were constructed and inoculated into BALB/c mice with or without pcDNA-IL-2 by using three different immunization routes (the intramuscular route, electroporation, or the oral route with live attenuated Salmonella enterica serovar Typhimurium). The cellular and humoral immune responses were assessed by enzyme-linked immunosorbent assays, lymphocyte proliferation assays, enzyme-linked immunospot assays, and fluorescence-activated cell sorter analyses. The results showed that specific humoral and cellular immunities could be induced in mice by inoculating them with SARS-CoV spike DNA vaccine alone or by coinoculation with IL-2-expressing plasmids. In addition, the immune response levels in the coinoculation groups were significantly higher than those in groups receiving the spike DNA vaccine alone. The comparison between the three vaccination routes indicated that oral vaccination evoked a vigorous T-cell response and a weak response predominantly with subclass immunoglobulin G2a (IgG2a) antibody. However, intramuscular immunization evoked a vigorous antibody response and a weak T-cell response, and vaccination by electroporation evoked a vigorous response with a predominant subclass IgG1 antibody response and a moderate T-cell response. Our findings show that the spike DNA vaccine has good immunogenicity and can induce specific humoral and cellular immunities in BALB/c mice, while IL-2 plays an immunoadjuvant role and enhances the humoral and cellular immune responses. Different vaccination routes also evoke distinct immune responses. This study provides basic information for the design of DNA vaccines against SARS-CoV.

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.

A glimpse into the diverse cellular immunity against SARS-CoV-2

2021 ◽  
Author(s):  
Cheng-Wei Chang ◽  
Yuchen Liu ◽  
Cheng Jiao ◽  
Hongwei Liu ◽  
Xiaochuan Chen ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Antibody Response ◽  
Cellular Immunity ◽  
Viral Antigens ◽  
Cellular Immune

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific cellular immune response may prove to be essential for long-term immune protection against the novel coronavirus disease 2019 (COVID-19). To assess COVID-19-specific immunity in the population, we synthesized selected peptide pools of SARS-CoV-2 structural and functional proteins, including Spike (S), Membrane (M), Envelope (E), Nucleocapsid (N) and Protease (P) as target antigens. Survey of the T cell precursur frequencies in healthy individuals specific to these viral antigens demonstrated a diverse cellular immunity, including high, medium, low and no responders. This was further confirmed by in vitro induction of anti-SARS-CoV-2 T cell immune responses using dendritic cell (DC)/T cell coculture, which supported the corresponding T cell precursor frequencies in each of the individuals tested. In general, the combination of all five viral antigen pools induced the strongest cellular immune response, yet individual donors responded differently to different viral antigens. Importantly, in vitro restimulation of the T cells with the DC-peptides induced increased anti-viral immune responses in all individuals even in the no responders, suggesting that repeated antigen stimulation could elicit a broad protection in immune naïve population. Our analysis recapitulates the critical role of cellular immunity in fighting COVID-19 and the importance of analyzing anti-SARS-CoV-2 T cell response in addition to antibody response in the population.ImportanceFacing the rapid evolving SARS-CoV-2 variants in the world, current emphasis on antibody-producing vaccines needs a quick revisit. The virus-specific cellular immunity may prove to be essential for long-term protection against COVID-19. This study designed a series of antigenic peptides encompassing the conserved and/or essential domains of Spike (S), Membrane (M), envelope (E), Nucleocapsid (N) and Protease (P) as targets to assess Covid-19-specific immunity in the population. The results demonstrated a diverse cellular immunity, including high, medium, low and no responders. This was verified by in vitro generation of anti-SARS-CoV-2 T-cells from these subjects. The study suggested that individuals responded differently to the different viral antigens, and importantly, repeated stimulation could produce virus specific T cells in all individuals, including the no responders. This study illustrates the needs for assessing anti-viral cellular immunity in addition to antibody response in the general population.

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.

scholarly journals The Mycobacterium tuberculosis Recombinant 27-Kilodalton Lipoprotein Induces a Strong Th1-Type Immune Response Deleterious to Protection

2003 ◽  
Vol 71 (6) ◽  
pp. 3146-3154 ◽  
Author(s):  
Avi-Hai Hovav ◽  
Jacob Mullerad ◽  
Liuba Davidovitch ◽  
Yolanta Fishman ◽  
Fabiana Bigi ◽  
...  
Keyword(s):  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Interleukin 10 ◽  
Control Groups ◽  
Cellular Immune Responses ◽  
Protective Antigens ◽  
Proliferation Response ◽  
Cellular Immune ◽  
Mycobacterial Antigens

ABSTRACT Th1 immune response is essential in the protection against mycobacterial intracellular pathogens. Lipoproteins trigger both humoral and cellular immune responses and may be candidate protective antigens. We studied in BALB/c mice the immunogenicity and the protection offered by the recombinant 27-kDa Mycobacterium tuberculosis lipoprotein and the corresponding DNA vaccine. Immunization with the 27-kDa antigen resulted in high titers of immunoglobulin G1 (IgG1) and IgG2a with a typical Th1 profile and a strong delayed hypersensitivity response. A strong proliferation response was observed in splenocytes, and significant nitric oxide production and gamma interferon secretion but not interleukin 10 secretion were measured. Based on these criteria, the 27-kDa antigen induced a typical Th1-type immune response thought to be necessary for protection. Surprisingly, in 27-kDa-vaccinated mice (protein or DNA vaccines) challenged by M. tuberculosis H37Rv or BCG strains, there was a significant increase in the numbers of CFU in the spleen compared to that for control groups. Furthermore, the protection provided by BCG or other mycobacterial antigens was completely abolished once the 27-kDa antigen was added to the vaccine preparations. This study indicates that the 27-kDa antigen has an adverse effect on the protection afforded by recognized vaccines. We are currently studying how the 27-kDa antigen modulates the mouse immune response.

scholarly journals Characterization of the Immune Response of MERS-CoV Vaccine Candidates Derived from Two Different Vectors in Mice

Viruses ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 125 ◽  
Author(s):  
Entao Li ◽  
Feihu Yan ◽  
Pei Huang ◽  
Hang Chi ◽  
Shengnan Xu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Antibody Response ◽  
Rabies Virus ◽  
Vaccine Development ◽  
Vaccine Candidate ◽  
Viral Vector ◽  
Vaccine Vector ◽  
Vaccine Candidates ◽  
Cellular Immune Responses ◽  
Cellular Immune

Middle East respiratory syndrome (MERS) is an acute, high-mortality-rate, severe infectious disease caused by an emerging MERS coronavirus (MERS-CoV) that causes severe respiratory diseases. The continuous spread and great pandemic potential of MERS-CoV make it necessarily important to develop effective vaccines. We previously demonstrated that the application of Gram-positive enhancer matrix (GEM) particles as a bacterial vector displaying the MERS-CoV receptor-binding domain (RBD) is a very promising MERS vaccine candidate that is capable of producing potential neutralization antibodies. We have also used the rabies virus (RV) as a viral vector to design a recombinant vaccine by expressing the MERS-CoV S1 (spike) protein on the surface of the RV. In this study, we compared the immunological efficacy of the vaccine candidates in BALB/c mice in terms of the levels of humoral and cellular immune responses. The results show that the rabies virus vector-based vaccine can induce remarkably earlier antibody response and higher levels of cellular immunity than the GEM particles vector. However, the GEM particles vector-based vaccine candidate can induce remarkably higher antibody response, even at a very low dose of 1 µg. These results indicate that vaccines constructed using different vaccine vector platforms for the same pathogen have different rates and trends in humoral and cellular immune responses in the same animal model. This discovery not only provides more alternative vaccine development platforms for MERS-CoV vaccine development, but also provides a theoretical basis for our future selection of vaccine vector platforms for other specific pathogens.

Sign in / Sign up

Export Citation Format

Share Document