scholarly journals Immune Responses to the HLA-A*0201-Restricted Epitopes of Tyrosinase and Glycoprotein 100 Enable Control of Melanoma Outgrowth in HLA-A*0201-Transgenic Mice

2001 ◽  
Vol 167 (9) ◽  
pp. 4853-4860 ◽  
Author(s):  
David W. Mullins ◽  
Timothy N. J. Bullock ◽  
Teresa A. Colella ◽  
Valentina V. Robila ◽  
Victor H. Engelhard
Keyword(s):  
Transgenic Mice ◽  
Immune Responses ◽  
Glycoprotein 100

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

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 DNA Immunization with Hepatitis C Virus (HCV) Polycistronic Genes or Immunization by HCV DNA Priming-Recombinant Canarypox Virus Boosting Induces Immune Responses and Protection from Recombinant HCV-Vaccinia Virus Infection in HLA-A2.1-Transgenic Mice

2003 ◽  
Vol 77 (1) ◽  
pp. 382-390 ◽  
Author(s):  
Preeti Pancholi ◽  
Marion Perkus ◽  
Nancy Tricoche ◽  
Qingyan Liu ◽  
Alfred M. Prince
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Transgenic Mice ◽  
Immune Responses ◽  
Vaccinia Virus ◽  
Target Cells ◽  
Dna Encoding ◽  
Recombinant Hcv ◽  
Hla A2.1 ◽  
Canarypox Virus

ABSTRACT We studied immune responses to hepatitis C virus (HCV) genes delivered as DNA encoding the entire HCV protein coding genome in two polycistronic plasmids encoding HCV capsid-E1-E2-NS2-NS3 and HCV NS3-NS4-NS5 in HLA-A2.1-transgenic mice. Immune responses to HCV DNA prime and recombinant canarypox virus boost were also studied with the above constructs. At 8 weeks after a canarypox virus boost, the DNA prime/canarypox virus boosting regimen induced potent cellular immune responses to HCV structural and nonstructural proteins on target cells expressing the HLA-A2.1 allele. High frequencies of gamma interferon-secreting cells, as detected by enzyme-linked immunospot assay, were obtained in response to several endogenously expressed HCV proteins. We also observed cytotoxic-T-lymphocyte reactivity in response to endogenously expressed HCV proteins in fresh spleen cells without in vitro expansion. Upon challenge with a recombinant vaccinia virus expressing HCV proteins at 2 months postimmunization, the HCV DNA prime/canarypox virus-immunized mice showed a complete reduction in vaccinia virus titers compared to HCV DNA prime/boost- and mock-immunized controls. Immune responses were still detectable 4 months after canarypox virus boost in immunized mice. Interestingly, at 10 months postimmunization (8 months after canarypox virus boost), the protection in HCV DNA prime/boost-immunized mice against recombinant HCV-vaccinia virus challenge was higher than that observed in HCV DNA prime/canarypox virus boost-immunized mice.

Endogenous galectin-3 expression levels modulate immune responses in galectin-3 transgenic mice

2015 ◽  
Vol 68 (2) ◽  
pp. 300-311 ◽  
Author(s):  
Aparna D. Chaudhari ◽  
Rajiv P. Gude ◽  
Rajiv D. Kalraiya ◽  
Shubhada V. Chiplunkar
Keyword(s):  
Transgenic Mice ◽  
Immune Responses ◽  
Expression Levels ◽  
Galectin 3

scholarly journals Differential Roles of Interleukin 15 mRNA Isoforms Generated by Alternative Splicing in Immune Responses in Vivo

2000 ◽  
Vol 191 (1) ◽  
pp. 157-170 ◽  
Author(s):  
Hitoshi Nishimura ◽  
Toshiki Yajima ◽  
Yoshikazu Naiki ◽  
Hironaka Tsunobuchi ◽  
Masayuki Umemura ◽  
...  
Keyword(s):  
T Cells ◽  
Alternative Splicing ◽  
Transgenic Mice ◽  
Immune Responses ◽  
Cd8 T Cells ◽  
Salmonella Infection ◽  
Mrna Isoforms ◽  
Interleukin 15 ◽  
Ifn Γ

At least two types of interleukin (IL)-15 mRNA isoforms are generated by alternative splicing at the 5′ upstream of exon 5 in mice. To elucidate the potential roles of IL-15 isoforms in immune responses in vivo, we constructed two groups of transgenic mice using originally described IL-15 cDNA with a normal exon 5 (normal IL-15 transgenic [Tg] mice) and IL-15 cDNA with an alternative exon 5 (alternative IL-15 Tg mice) under the control of an MHC class I promoter. Normal IL-15 Tg mice constitutionally produced a significant level of IL-15 protein and had markedly increased numbers of memory type (CD44high Ly6C+) of CD8+ T cells in the LN. These mice showed resistance to Salmonella infection accompanied by the enhanced interferon (IFN)-γ production, but depletion of CD8+ T cells exaggerated the bacterial growth, suggesting that the IL-15–dependent CD8+ T cells with a memory phenotype may serve to protect against Salmonella infection in normal IL-15 Tg mice. On the other hand, a large amount of intracellular IL-15 protein was detected but hardly secreted extracellularly in alternative IL-15 Tg mice. Although most of the T cells developed normally in the alternative IL-15 Tg mice, they showed impaired IFN-γ production upon TCR engagement. The alternative IL-15 transgenic mice were susceptible to Salmonella accompanied by impaired production of endogenous IL-15 and IFN-γ. Thus, two groups of IL-15 Tg mice may provide information concerning the different roles of IL-15 isoforms in the immune system in vivo.

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