scholarly journals Eucommia ulmoides Leaf Polysaccharide in Conjugation with Ovalbumin Act as Delivery System Can Improve Immune Response

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1384
Author(s):  
Haibo Feng ◽  
Jie Yang ◽  
Hui Zhi ◽  
Xin Hu ◽  
Yan Yang ◽  
...  

In this investigation, to maximize the desired immunoenhancement effects of PsEUL and stimulate an efficient humoral and cellular immune response against an antigen, PsEUL and the model antigen ovalbumin (OVA) were coupled using the N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC) reaction to yield a novel delivery system (PsEUL-OVA). The physicochemical characteristics and immune regulation effects of this new system were investigated. We found the yield of this EDC method to be 46.25%. In vitro, PsEUL-OVA (200 μg mL−1) could enhance macrophage proliferation and increase their phagocytic efficiency. In vivo, PsEUL-OVA could significantly increase the levels of OVA-specific antibody (IgG, IgG1, IgG2a, and IgG2b) titers and cytokine (IL-2, IL-4, IL-6, IFN-γ) levels. Additionally, it could activate T lymphocytes and facilitate the maturation of dendritic cells (DCs). These findings collectively suggested that PsEUL-OVA induced humoral and cellular immune responses by promoting the phagocytic activity of macrophages and DCs. Taken together, these results revealed that PsEUL-OVA had the potential to improve immune responses and provide a promising theoretical basis for the design of a novel delivery system.

Author(s):  
Nontobeko Thema ◽  
Alri Pretorius ◽  
Selaelo I. Tshilwane ◽  
Junita Liebenberg ◽  
Helena Steyn ◽  
...  

Secreted proteins are reported to induce cell-mediated immunity characterised by the production of interferon-gamma (IFN)-γ. In this study three open reading frames (ORFs) (Erum8060, Erum7760, Erum5000) encoding secreted proteins were selected from the Ehrlichia ruminantium (Welgevonden) genome sequence using bioinformatics tools to determine whether they induce a cellular immune response in vitro with mononuclear cells from needle and tick infected animals. The whole recombinant protein of the three ORFs as well as four adjacent fragments of the Erum5000 protein (Erum5000A, Erum5000B, Erum5000C, Erum5000D) were successfully expressed in a bacterial expression system which was confirmed by immunoblots using anti-His antibodies and sheep sera. These recombinant proteins were assayed with immune sheep and cattle peripheral blood mononuclear cells (PBMCs), spleen and lymph node (LN) cells to determine whether they induce recall cellular immune responses in vitro. Significant proliferative responses and IFN-γ production were evident for all recombinant proteins, especially Erum5000A, in both ruminant species tested. Thus overlapping peptides spanning Erum5000A were synthesised and peptides that induce proliferation of memory CD4+ and CD8+ T cells and production of IFN-γ were identified. These results illustrate that a Th1 type immune response was elicited and these recombinant proteins and peptides may therefore be promising candidates for development of a heartwater vaccine.


2020 ◽  
Author(s):  
naorem nihesh ◽  
Saikat Manna ◽  
Bradley Studnitzer ◽  
Jingjing Shen ◽  
Aaron Esser-Kahn

We developed a small-molecule trimeric PRR agonist-based adjuvant inspired by the stimulation pattern of a pathogen. This molecule generated by covalently linking TLR2/6 agonist, NOD2 agonist, and NLRP3 inflammasome activator, stimulates multiple subfamilies of PRRs in a spatially defined manner resulting in an amplified innate immune response <i>in vitro.</i> Moreover, it elicits both stronger humoral and cellular immune responses <i>in vivo</i>.


2020 ◽  
Author(s):  
naorem nihesh ◽  
Saikat Manna ◽  
Bradley Studnitzer ◽  
Jingjing Shen ◽  
Aaron Esser-Kahn

We developed a small-molecule trimeric PRR agonist-based adjuvant inspired by the stimulation pattern of a pathogen. This molecule generated by covalently linking TLR2/6 agonist, NOD2 agonist, and NLRP3 inflammasome activator, stimulates multiple subfamilies of PRRs in a spatially defined manner resulting in an amplified innate immune response <i>in vitro.</i> Moreover, it elicits both stronger humoral and cellular immune responses <i>in vivo</i>.


Vaccines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1408
Author(s):  
Qiao Li ◽  
Zhihua Liu ◽  
Yi Liu ◽  
Chen Liang ◽  
Jiayi Shu ◽  
...  

TFPR1 is a novel adjuvant for protein and peptide antigens, which has been demonstrated in BALB/c mice in our previous studies; however, its adjuvanticity in mice with different genetic backgrounds remains unknown, and its adjuvanticity needs to be improved to fit the requirements for various vaccines. In this study, we first compared the adjuvanticity of TFPR1 in two commonly used inbred mouse strains, BALB/c and C57BL/6 mice, in vitro and in vivo, and demonstrated that TFPR1 activated TLR2 to exert its immune activity in vivo. Next, to prove the feasibility of TFPR1 acting as a major component of combined adjuvants, we prepared a combined adjuvant, TF–Al, by formulating TFPR1 and alum at a certain ratio and compared its adjuvanticity with that of TFPR1 and alum alone using OVA and recombinant HBsAg as model antigens in both BALB/c and C57BL/6 mice. Results showed that TFPR1 acts as an effective vaccine adjuvant in both BALB/c mice and C57BL/6 mice, and further demonstrated the role of TLR2 in the adjuvanticity of TFPR1 in vivo. In addition, we obtained a novel combined adjuvant, TF–Al, based on TFPR1, which can augment antibody and cellular immune responses in mice with different genetic backgrounds, suggesting its promise for vaccine development in the future.


2002 ◽  
Vol 76 (12) ◽  
pp. 6093-6103 ◽  
Author(s):  
Eishiro Mizukoshi ◽  
Michelina Nascimbeni ◽  
Joshua B. Blaustein ◽  
Kathleen Mihalik ◽  
Charles M. Rice ◽  
...  

ABSTRACT The chimpanzee is a critical animal model for studying cellular immune responses to infectious pathogens such as hepatitis B and C viruses, human immunodeficiency virus, and malaria. Several candidate vaccines and immunotherapies for these infections aim at the induction or enhancement of cellular immune responses against viral epitopes presented by common human major histocompatibility complex (MHC) alleles. To identify and characterize chimpanzee MHC class I molecules that are functionally related to human alleles, we sequenced 18 different Pan troglodytes (Patr) alleles of 14 chimpanzees, 2 of them previously unknown and 3 with only partially reported sequences. Comparative analysis of Patr binding pockets and binding assays with biotinylated peptides demonstrated a molecular homology between the binding grooves of individual Patr alleles and the common human alleles HLA-A1, -A2, -A3, and -B7. Using cytotoxic T cells isolated from the blood of hepatitis C virus (HCV)-infected chimpanzees, we then mapped the Patr restriction of these HCV peptides and demonstrated functional homology between the Patr-HLA orthologues in cytotoxicity and gamma interferon (IFN-γ) release assays. Based on these results, 21 HCV epitopes were selected to characterize the chimpanzees' cellular immune response to HCV. In each case, IFN-γ-producing T cells were detectable in the blood after but not prior to HCV infection and were specifically targeted against those HCV peptides predicted by Patr-HLA homology. This study demonstrates a close functional homology between individual Patr and HLA alleles and shows that HCV infection generates HCV peptides that are recognized by both chimpanzees and humans with Patr and HLA orthologues. These results are relevant for the design and evaluation of vaccines in chimpanzees that can now be selected according to the most frequent human MHC haplotypes.


1988 ◽  
pp. 185-196
Author(s):  
Anne Durandy ◽  
Alain Fischer ◽  
Edouard Drouhet ◽  
Claude Griscelli

1999 ◽  
Vol 67 (11) ◽  
pp. 5567-5572 ◽  
Author(s):  
Félix Romain ◽  
Cynthia Horn ◽  
Pascale Pescher ◽  
Abdelkader Namane ◽  
Michel Riviere ◽  
...  

ABSTRACT A protection against a challenge with Mycobacterium tuberculosis is induced by previous immunization with living attenuated mycobacteria, usually bacillus Calmette-Guérin (BCG). The 45/47-kDa antigen complex (Apa) present in culture filtrates of BCG of M. tuberculosis has been identified and isolated based on its ability to interact mainly with T lymphocytes and/or antibodies induced by immunization with living bacteria. The protein is glycosylated. A large batch of Apa was purified from M. tuberculosis culture filtrate to determine the extent of glycosylation and its role on the expression of the immune responses. Mass spectrometry revealed a spectrum of glycosylated molecules, with the majority of species bearing six, seven, or eight mannose residues (22, 24, and 17%, respectively), while others three, four, or five mannoses (5, 9, and 14%, respectively). Molecules with one, two, or nine mannoses were rare (1.5, 3, and 3%, respectively), as were unglycosylated species (in the range of 1%). To eliminate the mannose residues linked to the protein, the glycosylated Apa molecules were chemically or enzymatically treated. The deglycosylated antigen was 10-fold less active than native molecules in eliciting delayed-type hypersensitivity reactions in guinea pigs immunized with BCG. It was 30-fold less active than native molecules when assayed in vitro for its capacity to stimulate T lymphocytes primed in vivo. The presence of the mannose residues on the Apa protein was essential for the antigenicity of the molecules in T-cell-dependent immune responses in vitro and in vivo.


2001 ◽  
Vol 69 (4) ◽  
pp. 2456-2461 ◽  
Author(s):  
Caroline Demangel ◽  
Umaimainthan Palendira ◽  
Carl G. Feng ◽  
Andrew W. Heath ◽  
Andrew G. D. Bean ◽  
...  

ABSTRACT The resolution of pulmonary tuberculosis (TB) critically depends on the development of the Th1 type of immune responses, as exemplified by the exacerbation of TB in IL-12-deficient mice. Therefore, vaccination strategies optimizing IL-12 production by antigen-presenting cells (APC) in response to mycobacteria may have enhanced protective efficacy. Since dendritic cells (DC) are the critical APC for activation of CD4+ and CD8+ T cells, we examined whether stimulation of Mycobacterium bovis bacillus Calmette Guérin (BCG)-infected DC via CD40 increased their ability to generate Th1-oriented cellular immune responses. Incubation of DC with an agonistic anti-CD40 antibody activated CD40 signaling in DC, as shown by increased expression of major histocompatibility complex class II and costimulatory molecules, mRNA production for proinflammatory cytokines and interleukin 12 (IL-12) p40. This activation pattern was maintained when DC were stimulated with anti-CD40 antibody and infected with BCG. Importantly, CD40-stimulated BCG-infected DC displayed increased capacity to release bioactive IL-12 and to activate gamma interferon (IFN-γ) producing T cells in vitro. Moreover, when C57BL/6 mice were immunized with these DC and challenged with aerosol Mycobacterium tuberculosis, increased levels of mRNA for IL-12 p40, IL-18, and IFN-γ were present in the draining mediastinal lymph nodes. However, the mycobacterial burden in the lungs was not reduced compared to that in mice immunized with BCG-infected non-CD40-stimulated DC. Therefore, although the manipulation of DC via CD40 is effective for enhancing immune responses to mycobacteria in vivo, additional strategies are required to increase protection against virulent M. tuberculosis infection.


2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
S. Viganò ◽  
M. Perreau ◽  
G. Pantaleo ◽  
A. Harari

The immune system has evolved to allow robust responses against pathogens while avoiding autoimmunity. This is notably enabled by stimulatory and inhibitory signals which contribute to the regulation of immune responses. In the presence of a pathogen, a specific and effective immune response must be induced and this leads to antigen-specific T-cell proliferation, cytokines production, and induction of T-cell differentiation toward an effector phenotype. After clearance or control of the pathogen, the effector immune response must be terminated in order to avoid tissue damage and chronic inflammation and this process involves coinhibitory molecules. When the immune system fails to eliminate or control the pathogen, continuous stimulation of T cells prevents the full contraction and leads to the functional exhaustion of effector T cells. Several evidences bothin vitroandin vivosuggest that this anergic state can be reverted by blocking the interactions between coinhibitory molecules and their ligands. The potential to revert exhausted or inactivated T-cell responses following selective blocking of their function made these markers interesting targets for therapeutic interventions in patients with persistent viral infections or cancer.


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