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

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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Prior dengue immunity enhances Zika virus infection of the maternal-fetal interface in rhesus macaques

10.1101/2021.01.25.428184 ◽

2021 ◽

Author(s):

C. M. Crooks ◽

A. M. Weiler ◽

S. L. Rybarczyk ◽

M. I. Bliss ◽

A. S. Jaeger ◽

...

Keyword(s):

Zika Virus ◽

Rhesus Macaques ◽

Maternal Plasma ◽

Adverse Outcomes ◽

Zikv Infection ◽

Primate Model ◽

Denv Serotypes ◽

The Impact ◽

Human Primate ◽

Maternal Fetal Interface

ABSTRACTConcerns have arisen that pre-existing immunity to dengue virus (DENV) could enhance Zika virus (ZIKV) disease, due to the homology between ZIKV and DENV and the observation of antibody-dependent enhancement (ADE) among DENV serotypes. To date, no study has examined the impact of pre-existing DENV immunity on ZIKV pathogenesis during pregnancy in a translational non-human primate model. Here we show that prior DENV-2 exposure enhanced ZIKV infection of maternal-fetal interface tissues in macaques. However, pre-existing DENV immunity had no detectable impact on ZIKV replication kinetics in maternal plasma, and all pregnancies progressed to term without adverse outcomes or gross fetal abnormalities detectable at delivery. Understanding the risks of ADE to pregnant women worldwide is critical as vaccines against DENV and ZIKV are developed and licensed and as DENV and ZIKV continue to circulate.

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Previous exposure to dengue virus is associated with increased Zika virus burden at the maternal-fetal interface in rhesus macaques

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0009641 ◽

2021 ◽

Vol 15 (7) ◽

pp. e0009641

Author(s):

Chelsea M. Crooks ◽

Andrea M. Weiler ◽

Sierra L. Rybarczyk ◽

Mason I. Bliss ◽

Anna S. Jaeger ◽

...

Keyword(s):

Dengue Virus ◽

Zika Virus ◽

Rhesus Macaques ◽

Maternal Plasma ◽

Adverse Outcomes ◽

Primate Model ◽

Denv Serotypes ◽

The Impact ◽

Human Primate ◽

Maternal Fetal Interface

Concerns have arisen that pre-existing immunity to dengue virus (DENV) could enhance Zika virus (ZIKV) disease, due to the homology between ZIKV and DENV and the observation of antibody-dependent enhancement (ADE) among DENV serotypes. To date, no study has examined the impact of pre-existing DENV immunity on ZIKV pathogenesis during pregnancy in a translational non-human primate model. Here we show that macaques with a prior DENV-2 exposure had a higher burden of ZIKV vRNA in maternal-fetal interface tissues as compared to DENV-naive macaques. However, pre-existing DENV immunity had no detectable impact on ZIKV replication kinetics in maternal plasma, and all pregnancies progressed to term without adverse outcomes or gross fetal abnormalities detectable at delivery. Understanding the risks of ADE to pregnant women worldwide is critical as vaccines against DENV and ZIKV are developed and licensed and as DENV and ZIKV continue to circulate.

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Characterization of baboon fetal membranes: Evaluation as a non-human primate model of fetal membrane rupture

Journal of the Society for Gynecologic Investigation ◽

10.1016/s1071-5576(97)86699-3 ◽

1998 ◽

Vol 5 (1) ◽

pp. 192A-192A

Author(s):

J MCLAREN ◽

S BELL ◽

A FAALEABAS

Keyword(s):

Fetal Membrane ◽

Fetal Membranes ◽

Primate Model ◽

Membrane Rupture ◽

Fetal Membrane Rupture ◽

Human Primate

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Cardiac Pacing in a Chronically Instrumented Non-Human Primate Model During Centrifuge,

10.21236/ada316940 ◽

1996 ◽

Author(s):

S. C. Koenig ◽

Craig Reister ◽

J. Schtaub ◽

Gary Muniz ◽

Tim Fergusan

Keyword(s):

Cardiac Pacing ◽

Primate Model ◽

Human Primate

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Combined therapy of mesenchymal stem cells with a GLP-1 receptor agonist, liraglutide, on an inflammatory-mediated diabetic non-human primate model

Life Sciences ◽

10.1016/j.lfs.2021.119374 ◽

2021 ◽

Vol 276 ◽

pp. 119374

Author(s):

Roghayeh Navabi ◽

Babak Negahdari ◽

Ensiyeh Hajizadeh-Saffar ◽

Mostafa Hajinasrollah ◽

Yaser Jenab ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Receptor Agonist ◽

Combined Therapy ◽

Primate Model ◽

Human Primate

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Neonatal Immune System Ontogeny: The Role of Maternal Microbiota and Associated Factors. How Might the Non-Human Primate Model Enlighten the Path?

Vaccines ◽

10.3390/vaccines9060584 ◽

2021 ◽

Vol 9 (6) ◽

pp. 584

Author(s):

Natalia Nunez ◽

Louis Réot ◽

Elisabeth Menu

Keyword(s):

Immune System ◽

Mode Of Delivery ◽

Microbial Colonization ◽

Therapeutic Interventions ◽

Primate Model ◽

Neonatal Immune System ◽

Gastrointestinal Colonization ◽

The Impact ◽

Human Primate

Interactions between the immune system and the microbiome play a crucial role on the human health. These interactions start in the prenatal period and are critical for the maturation of the immune system in newborns and infants. Several factors influence the composition of the infant’s microbiota and subsequently the development of the immune system. They include maternal infection, antibiotic treatment, environmental exposure, mode of delivery, breastfeeding, and food introduction. In this review, we focus on the ontogeny of the immune system and its association to microbial colonization from conception to food diversification. In this context, we give an overview of the mother–fetus interactions during pregnancy, the impact of the time of birth and the mode of delivery, the neonate gastrointestinal colonization and the role of breastfeeding, weaning, and food diversification. We further review the impact of the vaccination on the infant’s microbiota and the reciprocal case. Finally, we discuss several potential therapeutic interventions that might help to improve the newborn and infant’s health and their responses to vaccination. Throughout the review, we underline the main scientific questions that are left to be answered and how the non-human primate model could help enlighten the path.

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Combination therapy protects macaques against advanced Marburg virus disease

Nature Communications ◽

10.1038/s41467-021-22132-0 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Robert W. Cross ◽

Zachary A. Bornholdt ◽

Abhishek N. Prasad ◽

Viktoriya Borisevich ◽

Krystle N. Agans ◽

...

Keyword(s):

Combination Therapy ◽

Rhesus Monkeys ◽

Viral Infections ◽

Virus Disease ◽

Marburg Virus ◽

Therapeutic Window ◽

Post Inoculation ◽

Primate Model ◽

Lethal Infection ◽

Human Primate

AbstractMonoclonal antibodies (mAbs) and remdesivir, a small-molecule antiviral, are promising monotherapies for many viruses, including members of the genera Marburgvirus and Ebolavirus (family Filoviridae), and more recently, SARS-CoV-2. One of the major challenges of acute viral infections is the treatment of advanced disease. Thus, extending the window of therapeutic intervention is critical. Here, we explore the benefit of combination therapy with a mAb and remdesivir in a non-human primate model of Marburg virus (MARV) disease. While rhesus monkeys are protected against lethal infection when treatment with either a human mAb (MR186-YTE; 100%), or remdesivir (80%), is initiated 5 days post-inoculation (dpi) with MARV, no animals survive when either treatment is initiated alone beginning 6 dpi. However, by combining MR186-YTE with remdesivir beginning 6 dpi, significant protection (80%) is achieved, thereby extending the therapeutic window. These results suggest value in exploring combination therapy in patients presenting with advanced filovirus disease.

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