scholarly journals Engineering and characterization of a novel Self Assembling Protein for Toxoplasma peptide vaccine in HLA-A*11:01, HLA-A*02:01 and HLA-B*07:02 transgenic mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kamal El Bissati ◽  
Ying Zhou ◽  
Sara M. Paulillo ◽  
Senthil K. Raman ◽  
Christopher P. Karch ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Immune Responses ◽  
Peptide Vaccine ◽  
New Paradigm ◽  
Mouse Splenocytes ◽  
Peptide Epitopes ◽  
Self Assembling ◽  
Tlr4 Ligand ◽  
Chimeric Polypeptide ◽  
Vaccine Approach

Abstract Fighting smart diseases requires smart vaccines. Novel ways to present protective immunogenic peptide epitopes to human immune systems are needed. Herein, we focus on Self Assembling Protein Nanoparticles (SAPNs) as scaffolds/platforms for vaccine delivery that produce strong immune responses against Toxoplasma gondii in HLA supermotif, transgenic mice. Herein, we present a useful platform to present peptides that elicit CD4+, CD8+ T and B cell immune responses in a core architecture, formed by flagellin, administered in combination with TLR4 ligand-emulsion (GLA-SE) adjuvant. We demonstrate protection of HLA-A*11:01, HLA-A*02:01, and HLA-B*07:02 mice against toxoplasmosis by (i) this novel chimeric polypeptide, containing epitopes that elicit CD8+ T cells, CD4+ T helper cells, and IgG2b antibodies, and (ii) adjuvant activation of innate immune TLR4 and TLR5 pathways. HLA-A*11:01, HLA-A*02:01, and HLA-B*07:02q11 transgenic mouse splenocytes with peptides demonstrated predicted genetic restrictions. This creates a new paradigm-shifting vaccine approach to prevent toxoplasmosis, extendable to other diseases.

scholarly journals The Peptide Vaccine Combined with Prior Immunization of a Conventional Diphtheria-Tetanus Toxoid Vaccine Induced AmyloidβBinding Antibodies on Cynomolgus Monkeys and Guinea Pigs

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Akira Yano ◽  
Kaori Ito ◽  
Yoshikatsu Miwa ◽  
Yoshito Kanazawa ◽  
Akiko Chiba ◽  
...  
Keyword(s):  
Immune Responses ◽  
Tetanus Toxoid ◽  
Guinea Pigs ◽  
Peptide Vaccine ◽  
Cell Epitope ◽  
T Cell Epitope ◽  
Peptide Vaccination ◽  
Binding Profile ◽  
Cynomolgus Monkeys ◽  
The Brain

The reduction of brain amyloid beta (Aβ) peptides by anti-Aβantibodies is one of the possible therapies for Alzheimer’s disease. We previously reported that the Aβpeptide vaccine including the T-cell epitope of diphtheria-tetanus combined toxoid (DT) induced anti-Aβantibodies, and the prior immunization with conventional DT vaccine enhanced the immunogenicity of the peptide. Cynomolgus monkeys were given the peptide vaccine subcutaneously in combination with the prior DT vaccination. Vaccination with a similar regimen was also performed on guinea pigs. The peptide vaccine induced anti-Aβantibodies in cynomolgus monkeys and guinea pigs without chemical adjuvants, and excessive immune responses were not observed. Those antibodies could preferentially recognize Aβ40, and Aβ42compared to Aβfibrils. The levels of serum anti-Aβantibodies and plasma Aβpeptides increased in both animals and decreased the brain Aβ40level of guinea pigs. The peptide vaccine could induce a similar binding profile of anti-Aβantibodies in cynomolgus monkeys and guinea pigs. The peptide vaccination could be expected to reduce the brain Aβpeptides and their toxic effects via clearance of Aβpeptides by generated antibodies.

scholarly journals Implementation of Adenovirus-Mediated Pulmonary Expression of Human ACE2 in HLA Transgenic Mice Enables Establishment of a COVID-19 Murine Model for Assessment of Immune Responses to SARS-CoV-2 Infection

Pathogens ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 940
Author(s):  
Theodor Chitlaru ◽  
Erez Bar-Haim ◽  
Liat Bar-On ◽  
Shahar Rotem ◽  
Hila Cohen ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Immune Responses ◽  
Post Infection ◽  
High Reproducibility ◽  
Cellular Immune Responses ◽  
Loss Of Weight ◽  
Transient Loss ◽  
Different Strains ◽  
Cellular Immune ◽  
Human Specific

HLA transgenic mice are instrumental for evaluation of human-specific immune responses to viral infection. Mice do not develop COVID-19 upon infection with SARS-CoV-2 due to the strict tropism of the virus to the human ACE2 receptor. The aim of the current study was the implementation of an adenovirus-mediated infection protocol for human ACE2 expression in HLA transgenic mice. Transient pulmonary expression of the human ACE2 receptor in these mice results in their sensitisation to SARS-CoV-2 infection, consequently providing a valuable animal model for COVID-19. Infection results in a transient loss in body weight starting 3 days post-infection, reaching 20–30% loss of weight at day 7 and full recovery at days 11–13 post-infection. The evolution of the disease revealed high reproducibility and very low variability among individual mice. The method was implemented in two different strains of HLA immunized mice. Infected animals developed strong protective humoral and cellular immune responses specific to the viral spike-protein, strictly depending on the adenovirus-mediated human ACE2 expression. Convalescent animals were protected against a subsequent re-infection with SARS-CoV-2, demonstrating that the model may be applied for assessment of efficacy of anti-viral immune responses.

Th2 Immune Responses in GATA-3-Transgenic Mice Infected with Heligmosomoides polygyrus

2003 ◽  
Vol 131 (Suppl. 1) ◽  
pp. 11-14 ◽  
Author(s):  
Naohiro Watanabe ◽  
Hidekazu Tamauchi ◽  
Hideyuki Ozawa ◽  
Mamoru Ito ◽  
Zoltan Ovary ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Immune Responses ◽  
Heligmosomoides Polygyrus

Abstract 116: Detrimental Role of Toll-Like Receptor 4 in Cardiovirus-Induced Myocarditis

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Fumitaka Sato ◽  
Seiichi Omura ◽  
Nicholas E Martinez ◽  
Eiichiro Kawai ◽  
Ganta V Chaitanya ◽  
...  
Keyword(s):  
Immune Responses ◽  
Acute Phase ◽  
Viral Entry ◽  
Viral Myocarditis ◽  
Chronic Phase ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tlr4 Ligand ◽  
Ifn Γ ◽  
Deficient Mice

Picornavirus infections have been known as a leading cause of viral myocarditis in humans. Theiler’s murine encephalomyelitis virus (TMEV) belongs to the genus Cardiovirus, the family Picornaviridae and was reported to cause inflammation in the heart in one manuscript, while its pathomechanism is unclear. In viral myocarditis, viral replication in the heart and/or immune responses against virus as well as heart-antigen (autoimmunity) can contribute to the pathogenesis. Toll-like receptors (TLRs) are pattern recognition receptors (PRRs) that are important for recognizing pathogens as well as triggering innate immunity. Among TLRs, TLR4 has been demonstrated to play important roles in virus-mediated pathology: 1) TLR4 can contribute to viral entry in some viruses, 2) TLR4 may mediate tissue damage by anti-virus immune responses (immunopathology), 3) high levels of TLR4 expression were observed in the heart of patients with dilated cardiomyopathy following acute viral myocarditis, and 4) some viruses can bind to lipopolysaccharide (LPS), which is a TLR4 ligand. To determine the role of TLR4 in TMEV-induced myocarditis, we infected male C3H/HeJ (TLR4-deficient) and C3H/HeNtac (control TLR4+) mice with the DA strain of TMEV. We harvested the hearts and spleens on days 6 and 7 (acute phase) or days 63 and 64 (chronic phase) post-infection. Cardiac pathology was evaluated by hematoxylin and eosin staining and production of pro-inflammatory cytokines, interleukin (IL)-17A and interferon (IFN)-γ, from spleen cells was measured by an enzyme-linked immunosorbent assay (ELISA). In both mice, mild myocarditis was observed during the acute phase of TMEV infection. During the chronic phase, both mice developed severe pathology in the heart, including basophilic degeneration and calcification. However, the incidence of myocarditis was higher in control mice than TLR4-deficient mice. IL-17A and IFN-γ production was higher in control mice than in TLR4-deficient mice (control vs. TLR4-deficient mice, acute phase: IL-17A, 196 vs. 146 pg/ml; IFN-γ, 72 vs. 39 ng/ml; chronic phase: IL-17A, 290 vs. 229 pg/ml; IFN- γ, 142 vs. 88 ng/ml). These results suggest that TLR4 may be detrimental in TMEV-induced myocarditis by increasing pro-inflammatory cytokine production.

Immune responses of seven different “promiscuous” T-cell epitopes on chimeric peptide vaccine design

Peptides ◽  
1994 ◽  
pp. 732-733 ◽  
Author(s):  
A. M. DiGeorge ◽  
B. Wang ◽  
S. F. Kobs-Conrad ◽  
P. T. P. Kaumaya
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Peptide Vaccine ◽  
Vaccine Design ◽  
T Cell Epitopes ◽  
Chimeric Peptide

Synergistic effects of dual-presenting VEGF- and BDNF-mimetic peptide epitopes from self-assembling peptide hydrogels on peripheral nerve regeneration

Nanoscale ◽  
2019 ◽  
Vol 11 (42) ◽  
pp. 19943-19958 ◽  
Author(s):  
Jiaju Lu ◽  
Xiaoqing Yan ◽  
Xun Sun ◽  
Xuezhen Shen ◽  
Heyong Yin ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Synergistic Effects ◽  
Peripheral Nerve Regeneration ◽  
Mimetic Peptide ◽  
Peptide Epitopes ◽  
Self Assembling ◽  
Peptide Hydrogels

We developed the functionalized self-assembling peptide nanofiber hydrogel RAD/KLT/RGI that was dual-functionalized with VEGF- and BDNF-mimetic peptide epitopes for peripheral nerve regeneration.

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