Effect of human OX40 ligand fusion protein (MEDI6383) on immune cells of the humoral and cell-mediated immune response in a non-human primate model.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 3052-3052
Author(s):  
Michael D Oberst ◽  
Steven Eck ◽  
Nicholas Buss ◽  
Andrew Pierce ◽  
Haesun Park ◽  
...  
Keyword(s):  
Immune Response ◽  
Fusion Protein ◽  
Immune Cells ◽  
Primate Model ◽  
Cell Mediated Immune Response ◽  
Ox40 Ligand ◽  
Human Primate

scholarly journals Comparative Pathogenesis of Asian and African-Lineage Zika Virus in Indian Rhesus Macaque’s and Development of a Non-Human Primate Model Suitable for the Evaluation of New Drugs and Vaccines

2018 ◽  
Author(s):  
Jonathan O. Rayner ◽  
Raj Kalkeri ◽  
Scott Goebel ◽  
Zhaohui Cai ◽  
Brian Green ◽  
...  
Keyword(s):  
Immune Response ◽  
Zika Virus ◽  
Rhesus Macaques ◽  
New Drugs ◽  
Primate Model ◽  
Robust Immune Response ◽  
African Lineage ◽  
Limit Of Quantitation ◽  
Asian Lineage ◽  
Human Primate

The establishment of a well characterized non-human primate model of Zika virus (ZIKV) infection is critical for the development of medical interventions. In this study, challenging Indian rhesus macaques (IRMs) with ZIKV strains of the Asian lineage resulted in dose dependent peak viral loads between days 2 and 5 post infection; and a robust immune response which protected the animals from homologous and heterologous re-challenge. In contrast, viremia in IRMs challenged with an African lineage strain was below the assays lower limit of quantitation and the immune response was insufficient to protect from re-challenge. These results corroborate previous observations but are contrary to reports using other African strains obviating the need for additional studies to elucidate the variables contributing to the disparities. Nonetheless, the utility of an Asian lineage ZIKV IRM model for countermeasures development was verified by vaccinating animals with a formalin inactivated reference vaccine and demonstrating sterilizing immunity against a subsequent subcutaneous challenge.

Suppression of the Cell-Mediated Immune Response by a Fas-Immunoglobulin Fusion Protein

2006 ◽  
Vol 81 (7) ◽  
pp. 1041-1048 ◽  
Author(s):  
Yingnian Shen ◽  
Barbara Young ◽  
Mark L. Lipman
Keyword(s):  
Immune Response ◽  
Fusion Protein ◽  
Cell Mediated Immune Response

scholarly journals Comparative virulence of three different strains of Burkholderia pseudomallei in an aerosol non-human primate model

2021 ◽  
Vol 15 (2) ◽  
pp. e0009125
Author(s):  
Sylvia R. Trevino ◽  
Jennifer L. Dankmeyer ◽  
David P. Fetterer ◽  
Christopher P. Klimko ◽  
Jo Lynne W. Raymond ◽  
...  
Keyword(s):  
Immune Response ◽  
Disease Progression ◽  
Burkholderia Pseudomallei ◽  
Acute Infection ◽  
Elevated Serum ◽  
Clinical Signs ◽  
Acute Disease ◽  
Primate Model ◽  
Highly Virulent ◽  
Human Primate

Melioidosis, caused by the Gram-negative bacterium Burkholderia pseudomallei, is a major cause of sepsis and mortality in endemic regions of Southeast Asia and Northern Australia. B. pseudomallei is a potential bioterrorism agent due to its high infectivity, especially via inhalation, and its inherent resistance to antimicrobials. There is currently no vaccine for melioidosis and antibiotic treatment can fail due to innate drug resistance, delayed diagnosis and treatment, or insufficient duration of treatment. A well-characterized animal model that mimics human melioidosis is needed for the development of new medical countermeasures. This study first characterized the disease progression of melioidosis in the African green monkey (AGM) and rhesus macaque (RM) for non-human primate model down-selection. All AGMs developed acute lethal disease similar to that described in human acute infection following exposure to aerosolized B. pseudomallei strain HBPUB10134a. Only 20% of RMs succumbed to acute disease. Disease progression, immune response and pathology of two other strains of B. pseudomallei, K96243 and MSHR5855, were also compared using AGMs. These three B. pseudomallei strains represent a highly virulent strain from Thailand (HBPUB101034a), a highly virulent strains from Australia (MSHR5855), and a commonly used laboratory strains originating from Thailand (K96243). Animals were observed for clinical signs of infection and blood samples were analyzed for cytokine responses, blood chemistry and leukocyte changes in order to characterize bacterial infection. AGMs experienced fever after exposure to aerosolized B. pseudomallei at the onset of acute disease. Inflammation, abscesses and/or pyogranulomas were observed in lung with all three strains of B. pseudomallei. Inflammation, abscesses and/or pyogranulomas were observed in lymph nodes, spleen, liver and/or kidney with B. pseudomallei, HBPUB10134a and K96243. Additionally, the Australian strain MSHR5855 induced brain lesions in one AGM similar to clinical cases of melioidosis seen in Australia. Elevated serum levels of IL-1β, IL-1 receptor antagonist, IL-6, MCP-1, G-CSF, HGF, IFNγ, MIG, I-TAC, and MIP-1β at terminal end points can be significantly correlated with non-survivors with B. pseudomallei infection in AGM. The AGM model represents an acute model of B. pseudomallei infection for all three strains from two geographical locations and will be useful for efficacy testing of vaccines and therapeutics against melioidosis. In summary, a dysregulated immune response leading to excessive persistent inflammation and inflammatory cell death is the key driver of acute melioidosis. Early intervention in these pathways will be necessary to counter B. pseudomallei and mitigate the pathological consequences of melioidosis.

Evaluation of the host immune response to decellularized lung scaffolds derived from α-Gal knockout pigs in a non-human primate model

Biomaterials ◽  
2018 ◽  
Vol 187 ◽  
pp. 93-104 ◽  
Author(s):  
Elizabeth C. Stahl ◽  
Ryan W. Bonvillain ◽  
Clint D. Skillen ◽  
Brandon L. Burger ◽  
Hidetaka Hara ◽  
...  
Keyword(s):  
Immune Response ◽  
Host Immune Response ◽  
Primate Model ◽  
Human Primate

scholarly journals Evasion of the Cell-Mediated Immune Response by Alphaherpesviruses

Viruses ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1354
Author(s):  
Naoto Koyanagi ◽  
Yasushi Kawaguchi
Keyword(s):  
Immune Response ◽  
Natural Killer ◽  
Immune Evasion ◽  
Immune Cells ◽  
Target Cells ◽  
Latent Infections ◽  
Viral Propagation ◽  
Host Immune Responses ◽  
Cell Mediated Immune Response

Alphaherpesviruses cause various diseases and establish life-long latent infections in humans and animals. These viruses encode multiple viral proteins and miRNAs to evade the host immune response, including both innate and adaptive immunity. Alphaherpesviruses evolved highly advanced immune evasion strategies to be able to replicate efficiently in vivo and produce latent infections with recurrent outbreaks. This review describes the immune evasion strategies of alphaherpesviruses, especially against cytotoxic host immune responses. Considering these strategies, it is important to evaluate whether the immune evasion mechanisms in cell cultures are applicable to viral propagation and pathogenicity in vivo. This review focuses on cytotoxic T lymphocytes (CTLs), natural killer cells (NK cells), and natural killer T cells (NKT cells), which are representative immune cells that directly damage virus-infected cells. Since these immune cells recognize the ligands expressed on their target cells via specific activating and/or inhibitory receptors, alphaherpesviruses make several ligands that may be targets for immune evasion. In addition, alphaherpesviruses suppress the infiltration of CTLs by downregulating the expression of chemokines at infection sites in vivo. Elucidation of the alphaherpesvirus immune evasion mechanisms is essential for the development of new antiviral therapies and vaccines.

scholarly journals IMPACT OF TUMOR-DERIVED FACTORS ON DENDRITIC CELLS IN CANCER

2017 ◽  
Vol 16 (1) ◽  
pp. 12-23 ◽  
Author(s):  
A. A. Keskinov ◽  
M. R. Shurin ◽  
V. M. Bukhman ◽  
Z. S. Shprakh
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Dendritic Cells ◽  
Dendritic Cell ◽  
Tumor Microenvironment ◽  
Cancer Patients ◽  
Immune Cells ◽  
Humoral Immune ◽  
Cell Mediated Immune Response ◽  
Immune Response To Cancer

Dendritic cells play key role during tumorigenesis and immune response to it. They are able to uptake and present antigens to T cells, resulting in specific T cell mediated immune response. Furthermore, interaction between dendritic cells and other types of immune cells may boost cell-mediated and humoral immune response to cancer. Contrary to that, numerous tumor-derived factors may attract dendritic cells to neoplastic sites, causing impairment of their maturation, differentiation, and functional activity, resulting in deficiency of anti-tumor immune response or dendritic cell-mediated tolerance. Various factors within tumor microenvironment may either stimulate or inhibit dendritic cells and therefore need to be determined for improving efficacy of biotherapy utilizing dendritic cells. Meanwhile, recovery of dendritic cells functions in cancer patients remains one of primary aims for cancer immunotherapy. This review outlines main types of tumor-derived factors and their impact on dendritic cells in cancer.

scholarly journals Differentiation and Regulation of TH Cells: A Balancing Act for Cancer Immunotherapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Amrita Basu ◽  
Ganesan Ramamoorthi ◽  
Gabriella Albert ◽  
Corey Gallen ◽  
Amber Beyer ◽  
...  
Keyword(s):  
Immune Response ◽  
Cancer Immunotherapy ◽  
Immune Cells ◽  
Tumor Response ◽  
Cytotoxic T Cells ◽  
Cell Activity ◽  
Cytotoxic T Cell ◽  
Negative Effects ◽  
Cell Mediated Immune Response ◽  
Molecular Framework

Current success of immunotherapy in cancer has drawn attention to the subsets of TH cells in the tumor which are critical for activation of anti-tumor response either directly by themselves or by stimulating cytotoxic T cell activity. However, presence of immunosuppressive pro-tumorigenic TH subsets in the tumor milieu further contributes to the complexity of regulation of TH cell-mediated immune response. In this review, we present an overview of the multifaceted positive and negative effects of TH cells, with an emphasis on regulation of different TH cell subtypes by various immune cells, and how a delicate balance of contradictory signals can influence overall success of cancer immunotherapy. We focus on the regulatory network that encompasses dendritic cell-induced activation of CD4+ TH1 cells and subsequent priming of CD8+ cytotoxic T cells, along with intersecting anti-inflammatory and pro-tumorigenic TH2 cell activity. We further discuss how other tumor infiltrating immune cells such as immunostimulatory TH9 and Tfh cells, immunosuppressive Treg cells, and the duality of TH17 function contribute to tip the balance of anti- vs pro-tumorigenic TH responses in the tumor. We highlight the developing knowledge of CD4+ TH1 immune response against neoantigens/oncodrivers, impact of current immunotherapy strategies on CD4+ TH1 immunity, and how opposing action of TH cell subtypes can be explored further to amplify immunotherapy success in patients. Understanding the nuances of CD4+ TH cells regulation and the molecular framework undergirding the balancing act between anti- vs pro-tumorigenic TH subtypes is critical for rational designing of immunotherapies that can bypass therapeutic escape to maximize the potential of immunotherapy.

Sign in / Sign up

Export Citation Format

Share Document