A Pathogen Mimetic Molecule Induces Highly Amplified Synergistic Immune Activation to Vaccination via Activation of Multiple Signaling Pathways

Cellular Immune ◽

Multiple Signaling ◽

Stimulation Pattern

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>.

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

Pharmaceutics ◽

10.3390/pharmaceutics13091384 ◽

2021 ◽

Vol 13 (9) ◽

pp. 1384

Author(s):

Haibo Feng ◽

Jie Yang ◽

Hui Zhi ◽

Xin Hu ◽

Yan Yang ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Delivery System ◽

Physicochemical Characteristics ◽

Ethylcarbodiimide Hydrochloride ◽

Ifn Γ ◽

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.

A Combined Adjuvant TF–Al Consisting of TFPR1 and Aluminum Hydroxide Augments Strong Humoral and Cellular Immune Responses in Both C57BL/6 and BALB/c Mice

Vaccines ◽

10.3390/vaccines9121408 ◽

2021 ◽

Vol 9 (12) ◽

pp. 1408

Author(s):

Qiao Li ◽

Zhihua Liu ◽

Yi Liu ◽

Chen Liang ◽

Jiayi Shu ◽

...

Keyword(s):

Immune Responses ◽

Vaccine Development ◽

Inbred Mouse ◽

Effective Vaccine ◽

Mouse Strains ◽

Recombinant Hbsag ◽

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.

Mannan Antigen of Candida Albicans and Cellular Immune Responses in Vitro and in Vivo

Fungal Antigens ◽

10.1007/978-1-4613-0773-0_13 ◽

1988 ◽

pp. 185-196

Author(s):

Anne Durandy ◽

Alain Fischer ◽

Edouard Drouhet ◽

Claude Griscelli

Keyword(s):

Candida Albicans ◽

Immune Responses ◽

Stimulation of innate immune responses by malarial glycosylphosphatidylinositol via pattern recognition receptors

Parasitology ◽

10.1017/s0031182005008152 ◽

2005 ◽

Vol 130 (S1) ◽

pp. S45-S62 ◽

Cited By ~ 63

Author(s):

T. NEBL ◽

M. J. DE VEER ◽

L. SCHOFIELD

Keyword(s):

Pattern Recognition ◽

Immune Responses ◽

Molecular Mechanisms ◽

Severe Disease ◽

Pattern Recognition Receptors ◽

Innate Immune ◽

Proinflammatory Responses ◽

The glycosylphosphatidylinositol (GPI) anchor ofPlasmodium falciparumis thought to function as a critical toxin that contributes to severe malarial pathogenesis by eliciting the production of proinflammatory responses by the innate immune system of mammalian hosts. Analysis of the fine structure ofP. falciparumGPI suggests a requirement for the presence of both core glycan and lipid moieties in the recognition and signalling of parasite glycolipids by host immune cells. It has been demonstrated that GPI anchors of various parasitic protozoa can mediate cellular immune responses via members of the Toll-like family of pattern recognition receptors (TLRs). Recent studies indicate that GPI anchors ofP. falciparumand other protozoa are preferentially recognized by TLR-2, involving the MyD88-dependent activation of specific signalling pathways that mediate the production of proinflammatory cytokines and nitric oxide from host macrophagesin vitro. However, the contribution of malaria GPI toxin to severe disease syndromes and the role of specific TLRs or other pattern recognition receptors in innate immunityin vivois only just beginning to be characterized. A better understanding of the molecular mechanisms underlying severe malarial pathogenesis may yet lead to substantial new insights with important implications for the development of novel therapeutics for malaria treatment.

Deglycosylation of the 45/47-Kilodalton Antigen Complex of Mycobacterium tuberculosis Decreases Its Capacity To Elicit In Vivo or In Vitro Cellular Immune Responses

Infection and Immunity ◽

10.1128/iai.67.11.5567-5572.1999 ◽

1999 ◽

Vol 67 (11) ◽

pp. 5567-5572 ◽

Cited By ~ 66

Author(s):

Félix Romain ◽

Cynthia Horn ◽

Pascale Pescher ◽

Abdelkader Namane ◽

Michel Riviere ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

T Lymphocytes ◽

Immune Responses ◽

Delayed Type Hypersensitivity ◽

Antigen Complex ◽

Cellular Immune ◽

Living Bacteria

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.

Positive and Negative Regulation of Cellular Immune Responses in Physiologic Conditions and Diseases

Clinical and Developmental Immunology ◽

10.1155/2012/485781 ◽

2012 ◽

Vol 2012 ◽

pp. 1-11 ◽

Cited By ~ 27

Author(s):

S. Viganò ◽

M. Perreau ◽

G. Pantaleo ◽

A. Harari

Keyword(s):

Immune Response ◽

T Cells ◽

Immune System ◽

T Cell ◽

Immune Responses ◽

Viral Infections ◽

Therapeutic Interventions ◽

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.

Cellular immune responses induced in vitro by Ehrlichia ruminantium secreted proteins and identification of vaccine candidate peptides

Onderstepoort Journal of Veterinary Research ◽

10.4102/ojvr.v83i1.1170 ◽

2016 ◽

Vol 83 (1) ◽

Cited By ~ 5

Author(s):

Nontobeko Thema ◽

Alri Pretorius ◽

Selaelo I. Tshilwane ◽

Junita Liebenberg ◽

Helena Steyn ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Recombinant Proteins ◽

Mononuclear Cells ◽

Secreted Proteins ◽

Ehrlichia Ruminantium ◽

Ifn Γ ◽

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.

Correlation between in vivo humoral and in vitro cellular immune responses following immunization with hepatitis B surface antigen (HBsAg) vaccines

Vaccine ◽

10.1016/0264-410x(94)90290-9 ◽

1994 ◽

Vol 12 (9) ◽

pp. 812-818 ◽

Cited By ~ 44

Author(s):

G LEROUXROELS ◽

E VANHECKE ◽

W MICHIELSEN ◽

P VOET ◽

P HAUSER ◽

...

Keyword(s):

Hepatitis B ◽

Immune Responses ◽

Surface Antigen ◽

Hepatitis B Surface Antigen ◽

Humoral and cellular immune responses in sheep immunized with a 22 kilodalton exported protein of Mycobacterium avium subspecies paratuberculosis

Journal of Medical Microbiology ◽

10.1099/jmm.0.46785-0 ◽

2006 ◽

Vol 55 (12) ◽

pp. 1735-1740 ◽

Cited By ~ 14

Author(s):

Rachael C. Rigden ◽

Dakshina M. Jandhyala ◽

Chris Dupont ◽

Dianna Crosbie-Caird ◽

Nicolas Lopez-Villalobos ◽

...

Keyword(s):

Immune Responses ◽

Mycobacterium Avium ◽

Mycobacterium Avium Subspecies Paratuberculosis ◽

Specific Antibodies ◽

Antibody Recognition ◽

Exported Protein ◽

An immunogenic 22 kilodalton exported Mycobacterium avium subspecies paratuberculosis (MAP) lipoprotein (P22) was previously identified, and found to belong to the LppX/LprAFG family of mycobacterial lipoproteins. N-terminal polyhistidine-tagged P22 was produced and purified from Escherichia coli. Antibody recognition of P22, and interferon-gamma (IFN-γ) responses in vitro using blood from a sheep vaccinated with Neoparasec, confirmed its immunogenicity. To evaluate the immunogenicity of P22 in vivo, five sheep were immunized with a single dose containing 0.8 mg recombinant P22 protein in adjuvant. Blood was collected at 4, 13 and 29 weeks post-immunization (p.i.) and tested for anti-P22 antibodies and P22-specific IFN-γ production. P22-specific antibodies were detected by Western blot analysis in all five Neoparasec-immunized sheep at the three time points. Three out of five P22-immunized sheep produced P22-specific antibodies for up to 13 weeks p.i., and two gave a response at 29 weeks p.i. Recombinant P22 was able to stimulate significant IFN-γ production in blood of P22-immunized sheep at 13 and 29 weeks p.i. Recombinant P22 also elicited an IFN-γ response in blood of sheep immunized with Neoparasec.