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

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.

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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

10.20944/preprints201804.0096.v1 ◽

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.

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

Biomaterials ◽

10.1016/j.biomaterials.2018.09.038 ◽

2018 ◽

Vol 187 ◽

pp. 93-104 ◽

Cited By ~ 12

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

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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.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.15_suppl.3052 ◽

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

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A new and spontaneous animal model for ankylosing spondylitis is found in cynomolgus monkeys

10.21203/rs.3.rs-25995/v1 ◽

2020 ◽

Author(s):

Huanhuan JIA ◽

Meili CHEN ◽

Xiaoling LUO ◽

Gang HOU ◽

Ting LUO ◽

...

Keyword(s):

Ankylosing Spondylitis ◽

Bone Formation ◽

Disease Progression ◽

Joint Disease ◽

Pathological Examination ◽

Radiographic Examination ◽

Primate Model ◽

Cynomolgus Monkeys ◽

Abnormal Movements ◽

Human Primate

Abstract Background Ankylosing spondylitis (AS) is a progressive, disabling joint disease that affects millions worldwide. There is a lack of useful disease model to conduct comprehensive mechanistic studies. Non-human primate model is a potential spontaneous model for ankylosing spondylitis (AS). Methods A group of cynomolgus monkeys with abnormal joints and abnormal movements were screened out from about 20,000 cynomolgus monkeys primarily. A 2-years follow-up study of this group of cynomolgus monkeys having joint lesions reported of spinal stiffness was performed by conducting hematological testing, radiographic examination, family aggregation analysis, pathological analysis and genetic testing. Results These diseased animals suffered from spontaneous AS with clinical features recapitulating human AS disease progression. The spontaneous incidence rate and the onset age of AS in monkeys similar to epidemiological features of AS patients. The disease progression in disease monkeys have shown bone erosion, osteophyte formation and “Bamboo-like” change. ESR, CRP IL-17, TNF-α and VEGF levels significantly increase in AS monkeys comparing with normal monkeys. Several features similar to AS patients, including cartilage destruction, cartilage ossification, chondroid metaplasia and bone formation were shown in AS monkeys pathological examination results. Both the serum bone resorption and bone formation biomarkers of AS monkeys were significantly reduce. In our current SNP sequencing results, loci that similar to AS-relative SNPs in human genome have not yet been found. Conclusions The study offers a promising non-human primate model for spontaneous ankylosing spondylitis which may serve as an excellent substitute for its pre-clinical research.

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Chronic Alcohol Abuse and HIV Disease Progression: Studies with the Non-Human Primate Model

Current HIV Research ◽

10.2174/1570162x12666140721115717 ◽

2014 ◽

Vol 12 (4) ◽

pp. 243-253 ◽

Cited By ~ 12

Author(s):

Angela Amedee ◽

Whitney Nichols ◽

Spencer Robichaux ◽

Gregory Bagby ◽

Steve Nelson

Keyword(s):

Alcohol Abuse ◽

Disease Progression ◽

Hiv Disease ◽

Chronic Alcohol ◽

Primate Model ◽

Chronic Alcohol Abuse ◽

Human Primate

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363. Fetal Gene Therapy at 0.4G with AAV-hFIX or AAV-hFX Mediates Therapeutic Transgene Expression Despite Growth and a Positive Immune Response in a Non-Human Primate Model

Molecular Therapy ◽

10.1016/s1525-0016(16)34698-6 ◽

2013 ◽

Vol 21 ◽

pp. S139-S140

Keyword(s):

Gene Therapy ◽

Immune Response ◽

Transgene Expression ◽

Primate Model ◽

Positive Immune Response ◽

Human Primate

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Comparative Pathogenesis Of COVID-19, MERS And SARS In A Non-Human Primate Model

10.1101/2020.03.17.995639 ◽

2020 ◽

Cited By ~ 21

Author(s):

Barry Rockx ◽

Thijs Kuiken ◽

Sander Herfst ◽

Theo Bestebroer ◽

Mart M. Lamers ◽

...

Keyword(s):

Diffuse Alveolar Damage ◽

Clinical Signs ◽

Type I ◽

Primate Model ◽

Type Ii Pneumocytes ◽

Virus Excretion ◽

Cynomolgus Macaques ◽

Novel Coronavirus ◽

Nose And Throat ◽

Human Primate

AbstractA novel coronavirus, SARS-CoV-2, was recently identified in patients with an acute respiratory syndrome, COVID-19. To compare its pathogenesis with that of previously emerging coronaviruses, we inoculated cynomolgus macaques with SARS-CoV-2 or MERS-CoV and compared with historical SARS-CoV infections. In SARS-CoV-2-infected macaques, virus was excreted from nose and throat in absence of clinical signs, and detected in type I and II pneumocytes in foci of diffuse alveolar damage and mucous glands of the nasal cavity. In SARS-CoV-infection, lung lesions were typically more severe, while they were milder in MERS-CoV infection, where virus was detected mainly in type II pneumocytes. These data show that SARS-CoV-2 can cause a COVID-19-like disease, and suggest that the severity of SARS-CoV-2 infection is intermediate between that of SARS-CoV and MERS-CoV.One Sentence SummarySARS-CoV-2 infection in macaques results in COVID-19-like disease with prolonged virus excretion from nose and throat in absence of clinical signs.

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