scholarly journals Intradermal DNA Electroporation Induces Cellular and Humoral Immune Response and Confers Protection against HER2/neu Tumor

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Alessia Lamolinara ◽  
Lorenzo Stramucci ◽  
Albana Hysi ◽  
Manuela Iezzi ◽  
Cristina Marchini ◽  
...  
Keyword(s):  
Dna Vaccine ◽  
Mononuclear Cells ◽  
Humoral Response ◽  
Inflammatory Cells ◽  
Cell Types ◽  
Control Group ◽  
Intradermal Vaccination ◽  
Humoral Immune ◽  
Tumor Onset

Skin represents an attractive target for DNA vaccine delivery because of its natural richness in APCs, whose targeting may potentiate the effect of vaccination. Nevertheless, intramuscular electroporation is the most common delivery method for ECTM vaccination. In this study we assessed whether intradermal administration could deliver the vaccine into different cell types and we analyzed the evolution of tissue infiltrate elicited by the vaccination protocol. Intradermal electroporation (EP) vaccination resulted in transfection of different skin layers, as well as mononuclear cells. Additionally, we observed a marked recruitment of reactive infiltrates mainly 6–24 hours after treatment and inflammatory cells included CD11c+. Moreover, we tested the efficacy of intradermal vaccination against Her2/neu antigen in cellular and humoral response induction and consequent protection from a Her2/neu tumor challenge in Her2/neu nontolerant and tolerant mice. A significant delay in transplantable tumor onset was observed in both BALB/c (p≤0,0003) and BALB-neuT mice (p=0,003). Moreover, BALB-neuT mice displayed slow tumor growth as compared to control group (p<0,0016). In addition, while in vivo cytotoxic response was observed only in BALB/c mice, a significant antibody response was achieved in both mouse models. Our results identify intradermal EP vaccination as a promising method for delivering Her2/neu DNA vaccine.

scholarly journals Strong humoral response elicited by a DNA vaccine targeting gastrin-releasing peptide with optimized adjuvants inhibits murine prostate carcinoma growth in vivo

2009 ◽  
Vol 16 (4) ◽  
pp. 1171-1184 ◽  
Author(s):  
Yong Lu ◽  
Didier J L Mekoo ◽  
Kedong Ouyang ◽  
Xiangbing Hu ◽  
Yanhua Liu ◽  
...  
Keyword(s):  
Dna Vaccine ◽  
Cell Epitope ◽  
Humoral Response ◽  
Plasmid Vector ◽  
Antitumor Effects ◽  
Gastrin Releasing Peptide ◽  
Humoral Immune ◽  
Mycobacterial Hsp70 ◽  
Linear Alignment

Previous studies demonstrated that the elevated expression and receptor binding of gastrin-releasing peptide (GRP) in various types of cancer suggest that GRP might be a putative target for immunotherapy in neoplastic diseases. DNA vaccine for hormone/growth factor immune deprivation represents a feasible and attractive approach for cancer treatment; nevertheless, there is still a need to increase the potency of the DNA vaccine. Here, based on six copies of the B cell epitope GRP18–27 in a linear alignment as an immunogen, we designed several anti-GRP DNA vaccines containing different combinations of immunoadjuvants, such as HSP65, tetanus toxoid830–844 (T), pan HLA-DR-binding epitope (PADRE) (P), and mycobacterial HSP70407–426 (M), on a backbone of pCR3.1 plasmid vector with eight 5′-GACGTT-3′ CpG motifs and the VEGF183 signal peptide (VS). The effects of these immunoadjuvants in enhancing GRP-specific humoral immune response were then evaluated by comparing the respective immunogenicity and antitumor effects. Immunization of mice with pCR3.1-VS-HSP65-TP-GRP6-M2 elicited much higher levels of specific anti-GRP antibodies and more effectively inhibited the growth of a GRP-dependent tumor RM-1 in vivo. Interestingly, plasmids encoding for 2HSP70407–426, but not the one with 1 or 3HSP70407–426 showed stronger immune stimulatory potential as well as impressive antitumor activity, suggesting that 2HSP70407–426 is an efficient molecular adjuvant for developing self-epitope vaccines. The highly immunogenic, potent anti-tumorigenic and antiangiogenesis activities of the anti-GRP DNA vaccine offered a novel immunotherapeutic approach in the treatment of GRP-dependent tumors and their complications.

Abstract 1021: In Vivo Immune Response To Allogeneic Porcine Mesenchymal Stem Cell (msc) Transplantation: A 12-day Course Of Fk-506 Abbrogates Humoral Response.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Alain J Poncelet ◽  
Johnatan Vercruysse ◽  
Alain Saliez ◽  
Pierre Gianello
Keyword(s):  
Stem Cell ◽  
Humoral Response ◽  
Control Group ◽  
Blood Levels ◽  
Study Group ◽  
Fk 506 ◽  
Allogeneic Mscs ◽  
Cytotoxic Response ◽  
Humoral Responses

Purpose Several reports have highlighted the low immunogenic profile of MSCs. Therefore, we decided to test in vivo the humoral response to allogeneic MSCs transplantation and the effect of transient immunosuppression in a porcine model. Methods/Material MHC-controlled mini-swine SLA cd and SLA dd were used as donor and recipients, respectively. Two sites of transplantation were selected: subcutaneous and intracardiac. In our control group (n = 5), animals received no immunosuppression. In the study group (n = 11), nearly 1 x 10 6 allogeneic MSC/kg were injected. FK-506 was given from day 0 –12 and adjusted to therapeutic blood levels. Sera were serially collected up to one year after transplantation. The presence of specific anti-donor IgM and IgG was tested by flow cytometry and by a complement-mediated cytotoxicity assay. Results In the control group, all animals developed humoral responses in both IgM/G classes that persisted up to ten weeks. When transplanted subcutaneously, a single injection failed to elicit a complement-mediated cytotoxic response but subsequent re-challenge did. In the study group, only 2/11 FK-treated animals developed a transient humoral response, both in IgM and IgG, whereas all others failed to develop donor-specific antibodies. However, none of the sera tested from those 11 animals could elicit a complement-mediated cytotoxic response. Conclusion Allogeneic MSCs injected subcutaneously or intra-cardially can elicit prolonged humoral responses despite their putative low immunogenic profile. As already shown for experimental allogeneic organ transplantation, a transient immunosuppressive regimen can overcome the initial B cell response. Our result suggests that in vitro and in vivo characteristics of MSCs might differ and emphasizes the importance of pursuing research on allogeneic stem cell transplantation.

scholarly journals 3-Pentylcatechol, a Non-Allergenic Urushiol Derivative, Displays Anti-Helicobacter pylori Activity In Vivo

2020 ◽  
Vol 13 (11) ◽  
pp. 384
Author(s):  
Hang Yeon Jeong ◽  
Tae Ho Lee ◽  
Ju Gyeong Kim ◽  
Sueun Lee ◽  
Changjong Moon ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Triple Therapy ◽  
Inflammatory Cells ◽  
Control Group ◽  
Vitro Assay ◽  
Low Concentrations ◽  
H Pylori ◽  
Stomach Mucous Membrane

We previously reported that 3-pentylcatechol (PC), a synthetic non-allergenic urushiol derivative, inhibited the growth of Helicobacter pylori in an in vitro assay using nutrient agar and broth. In this study, we aimed to investigate the in vivo antimicrobial activity of PC against H. pylori growing in the stomach mucous membrane. Four-week-old male C57BL/6 mice (n = 4) were orally inoculated with H. pylori Sydney Strain-1 (SS-1) for 8 weeks. Thereafter, the mice received PC (1, 5, and 15 mg/kg) and triple therapy (omeprazole, 0.7 mg/kg; metronidazole, 16.7 mg/kg; clarithromycin, 16.7 mg/kg, reference groups) once daily for 10 days. Infiltration of inflammatory cells in gastric tissue was greater in the H. pylori-infected group compared with the control group and lower in both the triple therapy- and PC-treated groups. In addition, upregulation of cytokine mRNA was reversed after infection, upon administration of triple therapy and PC. Interestingly, PC was more effective than triple therapy at all doses, even at 1/15th the dose of triple therapy. In addition, PC demonstrated synergism with triple therapy, even at low concentrations. The results suggest that PC may be more effective against H. pylori than established antibiotics.

scholarly journals The expression of an intraspecific aggressive reaction in the face of a stressor agent alters the immune response in rats

2005 ◽  
Vol 65 (2) ◽  
pp. 203-209 ◽  
Author(s):  
J. M. Barreto-Medeiros ◽  
E. G. Feitoza ◽  
K. Magalhães ◽  
R. R. da Silva ◽  
F. M. Manhães-de-Castro ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Humoral Response ◽  
Aggressive Response ◽  
Control Group ◽  
Blood Samples ◽  
Humoral Immune ◽  
The Face ◽  
Intraspecific Aggressiveness ◽  
Specific Humoral Response

The repercussion on the immune response of the expression of intraspecific aggressiveness in the face of a stressor agent was investigated in rats. Ninety-day-old animals were divided into three groups: the control group (only immunological measurements were performed), the foot-shock (FS) (animals individually receiving FS), and the intraspecific aggressive response (IAR) group (animals receiving FS and presenting IAR). For immunological measurements, blood samples were collected promptly at 7 and 15 days after FS or IAR. The FS reduced the total leukocyte amount presented. However, aggressiveness triggered not only reduction of the leukocytes, but also lymphocyte decrease and neutrophil increase. Moreover, an elevation in total leukocytes associated with an increase in the humoral immune response was also observed one week after IAR. In this study, the expression of intraspecific aggressiveness in the face of a stressor seemed to activate the immune system and to potentiate the antigen specific humoral response.

scholarly journals CD4-Negative Cells Bind Human Immunodeficiency Virus Type 1 and Efficiently Transfer Virus to T Cells

2000 ◽  
Vol 74 (18) ◽  
pp. 8550-8557 ◽  
Author(s):  
Gene G. Olinger ◽  
Mohammed Saifuddin ◽  
Gregory T. Spear
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Mononuclear Cells ◽  
Cell Types ◽  
Virus Binding ◽  
Peripheral Blood Mononuclear ◽  
Human Immunodeficiency Virus Strain ◽  
Immunodeficiency Virus

ABSTRACT The ability of human immunodeficiency virus strain MN (HIVMN), a T-cell line-adapted strain of HIV, and X4 and R5 primary isolates to bind to various cell types was investigated. In general, HIVMN bound to cells at higher levels than did the primary isolates. Virus bound to both CD4-positive (CD4+) and CD4-negative (CD4−) cells, including neutrophils, Raji cells, tonsil mononuclear cells, erythrocytes, platelets, and peripheral blood mononuclear cells (PBMC), although virus bound at significantly higher levels to PBMC. However, there was no difference in the amount of HIV that bound to CD4-enriched or CD4-depleted PBMC. Virus bound to CD4− cells was up to 17 times more infectious for T cells in cocultures than was the same amount of cell-free virus. Virus bound to nucleated cells was significantly more infectious than virus bound to erythrocytes or platelets. The enhanced infection of T cells by virus bound to CD4− cells was not due to stimulatory signals provided by CD4− cells or infection of CD4− cells. However, anti-CD18 antibody substantially reduced the enhanced virus replication in T cells, suggesting that virus that bound to the surface of CD4−cells is efficiently passed to CD4+ T cells during cell-cell adhesion. These studies show that HIV binds at relatively high levels to CD4− cells and, once bound, is highly infectious for T cells. This suggests that virus binding to the surface of CD4− cells is an important route for infection of T cells in vivo.

scholarly journals Characterization of the Cellular Reaction to a Collagen-Based Matrix: An In Vivo Histological and Histomorphometrical Analysis

Materials ◽  
2020 ◽  
Vol 13 (12) ◽  
pp. 2730 ◽  
Author(s):  
Samuel Ebele Udeabor ◽  
Carlos Herrera-Vizcaíno ◽  
Robert Sader ◽  
C. James Kirkpatrick ◽  
Sarah Al-Maawi ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Ex Vivo ◽  
Test Group ◽  
Tissue Reaction ◽  
Implantation Site ◽  
Control Group ◽  
The Matrix ◽  
Tissue Reactions ◽  
Post Implantation

The permeability and inflammatory tissue reaction to Mucomaix® matrix (MM), a non- cross-linked collagen-based matrix was evaluated in both ex vivo and in vivo settings. Liquid platelet rich fibrin (PRF), a blood concentrate system, was used to assess its capacity to absorb human proteins and interact with blood cells ex vivo. In the in vivo aspect, 12 Wister rats had MM implanted subcutaneously, whereas another 12 rats (control) were sham-operated without biomaterial implantation. On days 3, 15 and 30, explantation was completed (four rats per time-point) to evaluate the tissue reactions to the matrix. Data collected were statistically analyzed using analysis of variance (ANOVA) and Tukey multiple comparisons tests (GraphPad Prism 8). The matrix absorbed the liquid PRF in the ex vivo study. Day 3 post-implantation revealed mild tissue inflammatory reaction with presence of mononuclear cells in the implantation site and on the biomaterial surface (mostly CD68-positive macrophages). The control group at this stage had more mononuclear cells than the test group. From day 15, multinucleated giant cells (MNGCs) were seen in the implantation site and the outer third of the matrix with marked increase on day 30 and spread to the matrix core. The presence of these CD68-positive MNGCs was associated with significant matrix vascularization. The matrix degraded significantly over the study period, but its core was still visible as of day 30 post-implantation. The high permeability and fast degradation properties of MM were highlighted.

scholarly journals Efficacy of Clarithromycin against Experimentally Induced Pneumonia Caused by Clarithromycin-Resistant Haemophilus influenzae in Mice

2009 ◽  
Vol 54 (2) ◽  
pp. 757-762 ◽  
Author(s):  
Shigeki Nakamura ◽  
Katsunori Yanagihara ◽  
Nobuko Araki ◽  
Koichi Yamada ◽  
Yoshitomo Morinaga ◽  
...  
Keyword(s):  
Haemophilus Influenzae ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Drug Susceptibility ◽  
Control Group ◽  
Inflammatory Protein ◽  
Conventional Drug ◽  
Good Penetration ◽  
Susceptibility Tests

ABSTRACT Clarithromycin is a 14-member lactone ring macrolide with potent activity against Haemophilus influenzae, including ampicillin-resistant strains. We evaluated the in vivo efficacy of clarithromycin at 40 mg/day and 100 mg/day for 3 days in the treatment of a murine model of pneumonia using a macrolide-resistant H. influenzae strain, which was also ampicillin resistant. The MIC of clarithromycin was 64 μg/ml. The viable bacterial counts in infected tissues after treatment with 100 mg clarithromycin/kg of body weight were lower than the counts obtained in control and 40-mg/kg clarithromycin-treated mice. The concentrations of macrophage inflammatory protein 2 (MIP-2) and interleukin 1β (IL-1β) in bronchoalveolar lavage fluid (BALF) samples from mice treated at both concentrations were lower than in the control group. Pathologically, following infection, clarithromycin-treated mice, particularly at a dose of 100 mg/kg, showed lower numbers of neutrophils in alveolar walls, and inflammatory changes had apparently improved, whereas large aggregates of inflammatory cells were observed within the alveoli of control mice. In addition, we demonstrated that clarithromycin has bacteriological effects against intracellular bacteria at levels below the MIC. Our results indicate that clarithromycin may be useful in vivo for macrolide-resistant H. influenzae, and this phenomenon may be related to the good penetration of clarithromycin into bronchoepithelial cells. We also believe that conventional drug susceptibility tests may not reflect the in vivo effects of clarithromycin.

Lymphodepletion Followed by Donor Lymphocyte Infusions (DLI) Causes Significantly More Acute Graft Versus Host Disease Than DLI Alone.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 260-260
Author(s):  
Jeffrey S. Miller ◽  
Daniel J. Weisdorf ◽  
Linda J. Burns ◽  
Arne Slungaard ◽  
John E. Wagner ◽  
...  
Keyword(s):  
Immune Activation ◽  
Acute Gvhd ◽  
Mononuclear Cells ◽  
Remission Induction ◽  
Control Group ◽  
Immune Reactivity ◽  
Cell Dose ◽  
Grade Iii ◽  
Donor Lymphocyte Infusions

Abstract Donor lymphocyte infusions (DLI) can produce lasting remissions in patients with relapsed CML after allogeneic HCT, but are less effective in other non-CML diseases. We hypothesized that in vivo expansion of DLI may enhance their anti-leukemia effects. Mouse adoptive transfer experiments show that up-front lymphodepletion improves in vivo lymphocyte expansion by providing lymphoid space, eliminating host anti-donor immune reactivity and by decreasing competition for growth factors that promote lymphocyte expansion. In this clinical trial, lymphodepletion was achieved with IV cyclophosphamide (Cy) 50 mg/kg once on day −6 and fludarabine (Flu) 25 mg/m2 for five consecutive days (−6 to −2), a regimen we have shown previously to result in an in vivo surge of IL-15. DLI was given 48 hours after the last Flu dose and consisted of mononuclear cells (adjusted to a T-cell dose of 1 x 108/kg). Fifteen patients with relapsed non-CML disease received Cy/Flu/DLI as their first treatment of relapse between 2004 and 2006. CML patients who received the same cell dose (n=28) or non-CML patients (n=35) who received a higher dose consisting of 3 daily lymphapheresis products treated from 1993–2003 were used as controls. Since there was no difference in GVHD rates between CML and non-CML patients, they were grouped together as one control group. While most control patients did not have significant leukocytopenia and were treated as outpatients, the patients receiving Cy/Flu/DLI all became lymphopenic and neutropenic by the time DLI were infused and were treated in the hospital. Patients who received Cy/Flu/DLI developed significantly more overall (60% vs. 24%, P=0.01) and grade III-IV acute GVHD (47% vs. 14%, P= 0.01) compared to controls. The interval from DLI to grade III-IV GVHD was modestly shorter in Cy/Flu/DLI patients compared to controls (mean = 17 days vs. 34 days; P=.19). In Cy/Flu/DLI patients, blood lymphocytes were collected before and at 14 days, 28 days, and 2 months after DLI for immunophenotyping. Proliferating T-cells, as measured by expression of the Ki67 marker, were significantly increased 14 days after DLI (10.3±2.8%) compared to baseline pre-DLI (1.6±0.6%, P=0.012), and were already returning to baseline levels 28 days after DLI (3.5±1.2%, P=0.19). Despite aggressive therapy, 4 of the 7 patients who developed grade III-IV GVHD died from complications of GVHD, suggesting that Cy/Flu/DLI induces immune activation that is sufficiently potent to enhance toxicity. Therefore, a decreased DLI dose (half) is currently being used in subsequent patients. These data show “proof of concept” that DLI following lymphodepleting chemotherapy leads to in vivo lymphocyte expansion and results in more severe GVHD than when giving patients DLI alone. The ability of lymphodepletion to enhance the immune effects of DLI is promising if alloreactivity correlates with remission induction. This strategy warrants further study to understand if the increased severity of acute GVHD leads to more complete or prolonged disease control and whether the immune activation can be controlled with lower cell doses.

scholarly journals Oncogene expression in autoimmune and normal peripheral blood mononuclear cells.

1986 ◽  
Vol 163 (5) ◽  
pp. 1292-1307 ◽  
Author(s):  
D M Klinman ◽  
J F Mushinski ◽  
M Honda ◽  
Y Ishigatsubo ◽  
J D Mountz ◽  
...  
Keyword(s):  
B Cells ◽  
Mononuclear Cells ◽  
Cell Types ◽  
Isolated Cells ◽  
Peripheral Blood Mononuclear ◽  
Normal Peripheral Blood ◽  
Additional Cell ◽  
Normal Controls

PBMC from patients with autoimmune diseases and from normal controls were studied for the expression of several cellular oncogenes. Gene expression was assessed by Northern blot analysis of poly(A)+ RNA obtained from leukapheresis samples. Patients with SLE expressed significantly more c-myc protooncogene RNA than did normal controls. Increased expression of the N-ras protooncogene was found in that subset of patients whose autoimmune disease was very active. Cells from individuals with SLE, but not from those with other autoimmune illnesses, showed significantly decreased levels of the c-myb and c-fos protooncogenes. To examine the implications of these findings, B and T cells were purified from apheresis samples donated by normal volunteers. When mitogen was used to activate the B cells in vitro, their pattern of protooncogene expression changed to resemble that found in freshly isolated cells from lupus patients. These results suggest that the differences detected in the expression of protooncogenes by patients with SLE may be due to the abnormal activation of their B cells in vivo. The pattern of protooncogene expression found in patients with other autoimmune illnesses is consistent with the activation of additional cell types in those diseases.

scholarly journals Systemic COVID-19 vaccination also enhances the humoral immune response after SARS CoV-2 infection in the population of an oncology hospital in Poland. Criteria for COVID-19 re-immunization are needed.

2021 ◽  
Author(s):  
Piotr Kosiorek ◽  
Dorota Kazberuk ◽  
Anna Hryniewicz ◽  
Robert Milewski ◽  
Samuel Stróż ◽  
...  
Keyword(s):  
Immune Response ◽  
Humoral Immune Response ◽  
Post Infection ◽  
Half Life ◽  
Humoral Response ◽  
Control Group ◽  
Igg Antibodies ◽  
Hospital Laboratory ◽  
Humoral Immune ◽  
Chemiluminescent Immunoassay

Abstract Systemic vaccination of the BNT162b2 mRNA stimulates humoral response. Our study aimed to compare the intensity of humoral immune response, measured by SARS CoV-2 IgG, SARS CoV-2 IgM, and neutralization S-RBD IgG antibodies level, post COVID-19 vaccination versus post-SARS COV-2 infection. We analysed 1060 people in the following groups: convalescents, healthy vaccinated, vaccinated with COMIRNATY, AstraZeneca, Moderna, Johnson & Johnson, and vaccinated SARS CoV-2 convalescents. A concentration of SARS CoV-2 IgG, SARS CoV-2 IgM, and neutralizing S-RBD IgG was estimated in hospital laboratory by chemiluminescent immunoassay - CLIA, MAGLUMI. Results: 1. We observed a rise of antibodies response in both convalescent SARS CoV-2 and COVID-19 vaccinated groups 2. The level of all antibodies’ concentrations in vaccinated COVID-19 convalescents was significantly higher. 3. We differentiated asymptomatic SARS CoV-2 convalescents from the control group. Based on our analysis, we suggest that it is essential to monitor SARS CoV-2 antibodies concentrations as an indicator of asymptomatic COVID-19 infection and equivalent to the effectiveness of humoral response in convalescents and vaccinated people. Considering the time-limited nature of the effects of post-infection SARS CoV-2 recovery or vaccination, among others physiological half-life, we suggested monitoring IgG antibodies level as a criterium for the next vaccination.

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