scholarly journals A Polylactide-Based Micellar Adjuvant Improves the Intensity and Quality of Immune Response

Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 107
Author(s):  
Myriam Lamrayah ◽  
Capucine Phelip ◽  
Céline Coiffier ◽  
Céline Lacroix ◽  
Thibaut Willemin ◽  
...  
Keyword(s):  
Immune Response ◽  
Near Infrared ◽  
Humoral Response ◽  
Elisa Test ◽  
Time Range ◽  
Micellar Systems ◽  
Hiv 1 ◽  
Gold Standards

Micelles from amphiphilic polylactide-block-poly(N-acryloxysuccinimide-co-N-vinylpyrrolidone) (PLA-b-P(NAS-co-NVP)) block copolymers of 105 nm in size were characterized and evaluated in a vaccine context. The micelles were non-toxic in vitro (both in dendritic cells and HeLa cells). In vitro fluorescence experiments combined with in vivo fluorescence tomography imaging, through micelle loading with the DiR near infrared probe, suggested an efficient uptake of the micelles by the immune cells. The antigenic protein p24 of the HIV-1 was successfully coupled on the micelles using the reactive N-succinimidyl ester groups on the micelle corona, as shown by SDS-PAGE analyses. The antigenicity of the coupled antigen was preserved and even improved, as assessed by the immuno-enzymatic (ELISA) test. Then, the performances of the micelles in immunization were investigated and compared to different p24-coated PLA nanoparticles, as well as Alum and MF59 gold standards, following a standardized HIV-1 immunization protocol in mice. The humoral response intensity (IgG titers) was substantially similar between the PLA micelles and all other adjuvants over an extended time range (one year). More interestingly, this immune response induced by PLA micelles was qualitatively higher than the gold standards and PLA nanoparticles analogs, expressed through an increasing avidity index over time (>60% at day 365). Taken together, these results demonstrate the potential of such small-sized micellar systems for vaccine delivery.

scholarly journals Effects of repetitive sevoflurane anaesthesia on immune response, select biochemical parameters and organ histology in mice

2003 ◽  
Vol 37 (3) ◽  
pp. 193-203 ◽  
Author(s):  
G. Elena ◽  
N. Amerio ◽  
P. Ferrero ◽  
M. L. Bay ◽  
J. Valenti ◽  
...  
Keyword(s):  
Immune Response ◽  
Renal Function ◽  
Peripheral Blood ◽  
Humoral Response ◽  
Peripheral Blood Leukocyte ◽  
Absolute Number ◽  
Sevoflurane Anaesthesia ◽  
Anaesthetic Procedure

Animal and technical models often require repeated anaesthetic administrations for surgical procedures. As there is evidence for immunomodulatory effects of anaesthesia, the effects of repeated exposure to sevoflurane anaesthesia on the immune response in mice were studied. Sevoflurane was administered in vivo under conditions that simulate those in clinical procedures. Adult male mice were anaesthetized with 3% sevoflurane in oxygen for 40 min weekly for 3 weeks. Untreated animals served as controls. After sevoflurane anaesthesia, peripheral blood leukocyte counts, the composition and in vitro function of spleen cells (lymphocytes and macrophages) and the in vivo immune response to a conventional T-dependent antigen were assessed. In addition, liver, spleen and kidney histopathology and also hepatic and renal function were studied. Three days after the latest anaesthetic procedure, the absolute number of both leukocyte and lymphocyte counts were reduced in peripheral blood. Splenic cell composition (LB, LTCD3+, LTCD4+ and LTCD8+), macrophage function and the mitogen-induced lymphoprolipherative response were preserved. Yet, the in vivo humoral response to a conventional antigen was augmented following the antigenic challenge. Assessment at day 9 after the last anaesthetic procedure revealed the persistence of the humoral response alteration. Nevertheless, sevoflurane-treated animals showed no evidence of histological changes or alteration in hepatic or renal function.

HIV-1 STRATEGIES OF IMMUNE EVASION

2005 ◽  
Vol 16 (12) ◽  
pp. 1869-1878 ◽  
Author(s):  
F. CASTIGLIONE ◽  
M. BERNASCHI
Keyword(s):  
Immune Response ◽  
Disease Progression ◽  
Computer Model ◽  
Immune Evasion ◽  
Selective Pressure ◽  
Computer Experiments ◽  
Replication Rate ◽  
Hiv 1

We simulate the progression of the HIV-1 infection in untreated host organisms. The phenotype features of the virus are represented by the replication rate, the probability of activating the transcription, the mutation rate and the capacity to stimulate an immune response (the so-called immunogenicity). It is very difficult to study in-vivo or in-vitro how these characteristics of the virus influence the evolution of the disease. Therefore we resorted to simulations based on a computer model validated in previous studies. We observe, by means of computer experiments, that the virus continuously evolves under the selective pressure of an immune response whose effectiveness downgrades along with the disease progression. The results of the simulations show that immunogenicity is the most important factor in determining the rate of disease progression but, by itself, it is not sufficient to drive the disease to a conclusion in all cases.

Platelet Derived CD154 Induced by Tat Contributes to HIV-1 Associated Autoimmune Thrombocytopenia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2669-2669
Author(s):  
Jianhui Wang ◽  
Wei Zhang ◽  
Zongdong Li
Keyword(s):  
Immune Response ◽  
Platelet Activation ◽  
Conflicts Of Interest ◽  
Calcium Flux ◽  
Tat Protein ◽  
Autoimmune Thrombocytopenia ◽  
Integrin Β3 ◽  
Hiv 1

Abstract Abstract 2669 Poster Board II-645 Enhanced platelet activation was reported in HIV-1 infected patients and strongly correlated with plasma viral load. The HIV-1 Tat protein is able to serve as a ligand of the integrin αvβ3 and several chemokine receptors (CCR2 and CCR3) and to induce downstream signaling in cells express those receptors but the effect of Tat on platelet activation has not been fully investigated yet. Activated platelets are known to express and release a variety of proteins that can modulate the immune system, and platelet derived CD154 is reportedly involved in the development of autoimmune thrombocytopenia. However, the full mechanism underlying HIV-1 induced platelet activation and the biological consequences are not completely understood. In this study, we demonstrate that Tat is able to interact with platelets and β3 integrin by S35 label Tat-platelet binding assay and GST-Tat protein pull-down. We then show that Tat is able to induce platelet activation, up-regulates both CD62P and CD154 in both mouse and human platelets, and results in micro-particle release (as demonstrated by electron microscopy). Tat induces greatly diminished activation in integrin β3 knock out platelets or in platelets pretreated with CCR3 or calcium flux inhibitors, suggesting the requirement of chemokine receptor CCR3, integrin β3 and calcium flux for Tat induced platelet activation. The effect of Tat induced platelet activation on the immune response was studied both in vitro and in vivo. An enhanced immunoglobulin class switch was found in mouse spleen B cells co-cultured with platelets treated with Tat in vitro. In addition, an early antibody response against adenovirus was found in Tat injected mouse immunized with adenovirus suggesting an enhanced immune response in vivo. Thus, we have described a new mechanism in which Tat is able to induce platelet activation and have generated a model in which platelet activation can contribute to the development of HIV-1 associated thrombocytopenia. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Immune Response of Drosophila suzukii Larvae to Infection with the Nematobacterial Complex Steinernema carpocapsae–Xenorhabdus nematophila

Insects ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 210 ◽  
Author(s):  
Anna Garriga ◽  
Maristella Mastore ◽  
Ana Morton ◽  
Fernando Garcia del Pino ◽  
Maurizio Francesco Brivio
Keyword(s):  
Immune Response ◽  
Entomopathogenic Nematodes ◽  
Humoral Response ◽  
Inhibitory Effect ◽  
Steinernema Carpocapsae ◽  
Invasive Pest ◽  
Xenorhabdus Nematophila ◽  
Drosophila Suzukii

Entomopathogenic nematodes have been proposed as biological agents for the control of Drosophila suzukii, an invasive pest of small-stone and soft-skinned fruits. Larvae of the fly are susceptible to Steinernema carpocapsae infection but the reaction of immune defenses of the host are unknown. To determine the immune response, larvae were infected with S. carpocapsae and Xenorhabdus nematophila to evaluate the effector mechanisms of both humoral and cellular processes. The symbiont bacteria presented an inhibitory effect on the phenoloxidase cascade with a low level of melanization. Besides, X. nematophila activated the synthesis of putative antimicrobial peptides on the hemolymph of infected larvae. However, those peptides presented a lower antimicrobial activity compared to hemolymph from larvae infected with non-symbiont bacteria. Xenorhabdus nematophila avoided also the phagocytosis response of hemocytes. During in vitro and in vivo assays, S. carpocapsae was not encapsulated by cells, unless the cuticle was damaged with a lipase-treatment. Hemocyte counts confirmed differentiation of lamellocytes in the early phase of infection despite the unrecognition of the nematodes. Both X. nematophila and S. carpocapsae avoided the cellular defenses of D. suzukii larvae and depressed the humoral response. These results confirmed the potential of entomopathogenic nematodes to control D. suzukii.

scholarly journals Induction of Long-Term Protective Antiviral Endogenous Immune Response by Short Neutralizing Monoclonal Antibody Treatment

2005 ◽  
Vol 79 (10) ◽  
pp. 6272-6280 ◽  
Author(s):  
Laurent Gros ◽  
Hanna Dreja ◽  
Anne Laure Fiser ◽  
Marc Plays ◽  
Mireia Pelegrin ◽  
...  
Keyword(s):  
Immune Response ◽  
Treatment Strategies ◽  
Humoral Response ◽  
Antiviral Effect ◽  
Adjunctive Treatment ◽  
Antibody Treatment ◽  
Antiviral Immune Response

ABSTRACT Long-term immune control of viral replication still remains a major challenge in retroviral diseases. Several monoclonal antibodies (MAbs) have already shown antiviral activities in vivo, including in the clinic but their effects on the immune system of treated individuals are essentially unknown. Using the lethal neurodegeneration induced in mice upon infection of neonates by the FrCasE retrovirus as a model, we report here that transient treatment by a neutralizing MAb shortly after infection can, after an immediate antiviral effect, favor the development of a strong protective host immune response containing viral propagation long after the MAb has disappeared. In vitro virus neutralization- and complement-mediated cell lysis assays, as well as in vivo viral challenges and serum transfer experiments, indicate a clear and essential contribution of the humoral response to antiviral protection. Our observation may have important therapeutic consequences as it suggests that short antibody-based therapies early after infection should be considered, at least in the case of maternally infected infants, as adjunctive treatment strategies against human immunodeficiency virus, not only for a direct effect on the viral load but also for favoring the emergence of an endogenous antiviral immune response.

scholarly journals B and T cells collaborate in antiviral responses via IL-6, IL-21, and transcriptional activator and coactivator, Oct2 and OBF-1

2012 ◽  
Vol 209 (11) ◽  
pp. 2049-2064 ◽  
Author(s):  
Alex Karnowski ◽  
Stephane Chevrier ◽  
Gabrielle T. Belz ◽  
Adele Mount ◽  
Dianne Emslie ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
B Cells ◽  
Cd4 T Cells ◽  
Humoral Response ◽  
Transcriptional Activator ◽  
Early Event ◽  
Tfh Cells

A strong humoral response to infection requires the collaboration of several hematopoietic cell types that communicate via antigen presentation, surface coreceptors and their ligands, and secreted factors. The proinflammatory cytokine IL-6 has been shown to promote the differentiation of activated CD4+ T cells into T follicular helper cells (TFH cells) during an immune response. TFH cells collaborate with B cells in the formation of germinal centers (GCs) during T cell–dependent antibody responses, in part through secretion of critical cytokines such as IL-21. In this study, we demonstrate that loss of either IL-6 or IL-21 has marginal effects on the generation of TFH cells and on the formation of GCs during the response to acute viral infection. However, mice lacking both IL-6 and IL-21 were unable to generate a robust TFH cell–dependent immune response. We found that IL-6 production in follicular B cells in the draining lymph node was an important early event during the antiviral response and that B cell–derived IL-6 was necessary and sufficient to induce IL-21 from CD4+ T cells in vitro and to support TFH cell development in vivo. Finally, the transcriptional activator Oct2 and its cofactor OBF-1 were identified as regulators of Il6 expression in B cells.

scholarly journals 1592U89, a novel carbocyclic nucleoside analog with potent, selective anti-human immunodeficiency virus activity.

1997 ◽  
Vol 41 (5) ◽  
pp. 1082-1093 ◽  
Author(s):  
S M Daluge ◽  
S S Good ◽  
M B Faletto ◽  
W H Miller ◽  
M H St Clair ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Oral Bioavailability ◽  
Human Peripheral Blood ◽  
Cross Resistance ◽  
Immunodeficiency Virus ◽  
Carbocyclic Nucleoside ◽  
Hiv 1 ◽  
In Cells

1592U89, (-)-(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclo pentene-1-methanol, is a carbocyclic nucleoside with a unique biological profile giving potent, selective anti-human immunodeficiency virus (HIV) activity. 1592U89 was selected after evaluation of a wide variety of analogs containing a cyclopentene substitution for the 2'-deoxyriboside of natural deoxynucleosides, optimizing in vitro anti-HIV potency, oral bioavailability, and central nervous system (CNS) penetration. 1592U89 was equivalent in potency to 3'-azido-3'-deoxythymidine (AZT) in human peripheral blood lymphocyte (PBL) cultures against clinical isolates of HIV type 1 (HIV-1) from antiretroviral drug-naive patients (average 50% inhibitory concentration [IC50], 0.26 microM for 1592U89 and 0.23 microM for AZT). 1592U89 showed minimal cross-resistance (approximately twofold) with AZT and other approved HIV reverse transcriptase (RT) inhibitors. 1592U89 was synergistic in combination with AZT, the nonnucleoside RT inhibitor nevirapine, and the protease inhibitor 141W94 in MT4 cells against HIV-1 (IIIB). 1592U89 was anabolized intracellularly to its 5'-monophosphate in CD4+ CEM cells and in PBLs, but the di- and triphosphates of 1592U89 were not detected. The only triphosphate found in cells incubated with 1592U89 was that of the guanine analog (-)-carbovir (CBV). However, the in vivo pharmacokinetic, distribution, and toxicological profiles of 1592U89 were distinct from and improved over those of CBV, probably because CBV itself was not appreciably formed from 1592U89 in cells or animals (<2%). The 5'-triphosphate of CBV was a potent, selective inhibitor of HIV-1 RT, with Ki values for DNA polymerases (alpha, beta, gamma, and epsilon which were 90-, 2,900-, 1,200-, and 1,900-fold greater, respectively, than for RT (Ki, 21 nM). 1592U89 was relatively nontoxic to human bone marrow progenitors erythroid burst-forming unit and granulocyte-macrophage CFU (IC50s, 110 microM) and human leukemic and liver tumor cell lines. 1592U89 had excellent oral bioavailability (105% in the rat) and penetrated the CNS (rat brain and monkey cerebrospinal fluid) as well as AZT. Having demonstrated an excellent preclinical profile, 1592U89 has progressed to clinical evaluation in HIV-infected patients.

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