scholarly journals Establishment of an African green monkey model for COVID-19

2020 ◽  
Author(s):  
Courtney Woolsey ◽  
Viktoriya Borisevich ◽  
Abhishek N. Prasad ◽  
Krystle N. Agans ◽  
Daniel J. Deer ◽  
...  
Keyword(s):  
Respiratory Disease ◽  
Nonhuman Primates ◽  
Rhesus Macaques ◽  
Human Condition ◽  
Monkey Model ◽  
Global Pandemic ◽  
Green Monkey ◽  
Virus Exposure ◽  
High Level ◽  
Green Monkeys

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for an unprecedented global pandemic of COVID-19. Animal models are urgently needed to study the pathogenesis of COVID-19 and to screen candidate vaccines and treatments. Nonhuman primates (NHP) are considered the gold standard model for many infectious pathogens as they usually best reflect the human condition. Here, we show that African green monkeys support a high level of SARS-CoV-2 replication and develop pronounced respiratory disease that may be more substantial than reported for other NHP species including cynomolgus and rhesus macaques. In addition, SARS-CoV-2 was detected in mucosal samples of all animals including feces of several animals as late as 15 days after virus exposure. Importantly, we show that virus replication and respiratory disease can be produced in African green monkeys using a much lower and more natural dose of SARS-CoV-2 than has been employed in other NHP studies.

scholarly journals UK B.1.1.7 variant exhibits increased respiratory replication and shedding in nonhuman primates

2021 ◽  
Author(s):  
Kyle Rosenke ◽  
Friederike Feldmann ◽  
Atsushi Okumura ◽  
Frederick Hansen ◽  
Tsing-Lee Tang-Huau ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Respiratory Tract ◽  
Respiratory Disease ◽  
Lower Respiratory Tract ◽  
Nonhuman Primates ◽  
Infectious Virus ◽  
Clinical Presentation ◽  
Viral Rna ◽  
The Uk ◽  
Green Monkeys

The continuing emergence of SARS-CoV-2 variants calls for regular assessment to identify differences in viral replication, shedding and associated disease. In this study, African green monkeys were infected intranasally with either a contemporary D614G or the UK B.1.1.7 variant. Both variants caused mild respiratory disease with no significant differences in clinical presentation. Significantly higher levels of viral RNA and infectious virus were found in upper and lower respiratory tract samples and tissues from B.1.1.7 infected animals. Interestingly, D614G infected animals showed significantly higher levels of viral RNA and infectious virus in rectal swabs and gastrointestinal tract tissues. Our results indicate that B.1.1.7 infection in African green monkeys is associated with increased respiratory replication and shedding but no disease enhancement similar to human B.1.1.7 cases.

scholarly journals The Two Major Human Metapneumovirus Genetic Lineages Are Highly Related Antigenically, and the Fusion (F) Protein Is a Major Contributor to This Antigenic Relatedness

2004 ◽  
Vol 78 (13) ◽  
pp. 6927-6937 ◽  
Author(s):  
Mario H. Skiadopoulos ◽  
Stéphane Biacchesi ◽  
Ursula J. Buchholz ◽  
Jeffrey M. Riggs ◽  
Sonja R. Surman ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Nonhuman Primates ◽  
Reciprocal Cross ◽  
F Protein ◽  
Genetic Lineages ◽  
Antigenic Relatedness ◽  
Cross Neutralization ◽  
High Level ◽  
Green Monkeys

ABSTRACT The growth properties and antigenic relatedness of the CAN98-75 (CAN75) and the CAN97-83 (CAN83) human metapneumovirus (HMPV) strains, which represent the two distinct HMPV genetic lineages and exhibit 5 and 63% amino acid divergence in the fusion (F) and attachment (G) proteins, respectively, were investigated in vitro and in rodents and nonhuman primates. Both strains replicated to high titers (≥6.0 log10) in the upper respiratory tract of hamsters and to moderate titers (≥3.6 log10) in the lower respiratory tract. The two lineages exhibited 48% antigenic relatedness based on reciprocal cross-neutralization assay with postinfection hamster sera, and infection with each strain provided a high level of resistance to reinfection with the homologous or heterologous strain. Hamsters immunized with a recombinant human parainfluenza virus type 1 expressing the fusion F protein of the CAN83 strain developed a serum antibody response that efficiently neutralized virus from both lineages and were protected from challenge with either HMPV strain. This result indicates that the HMPV F protein is a major antigenic determinant that mediates extensive cross-lineage neutralization and protection. Both HMPV strains replicated to low titers in the upper and lower respiratory tracts of rhesus macaques but induced high levels of HMPV-neutralizing antibodies in serum effective against both lineages. The level of HMPV replication in chimpanzees was moderately higher, and infected animals developed mild colds. HMPV replicated the most efficiently in the respiratory tracts of African green monkeys, and the infected animals developed a high level of HMPV serum-neutralizing antibodies (1:500 to 1:1,000) effective against both lineages. Reciprocal cross-neutralization assays in which postinfection sera from all three primate species were used indicated that CAN75 and CAN83 are 64 to 99% related antigenically. HMPV-infected chimpanzees and African green monkeys were highly protected from challenge with the heterologous HMPV strain. Taken together, the results from hamsters and nonhuman primates support the conclusion that the two HMPV genetic lineages are highly related antigenically and are not distinct antigenic subtypes or subgroups as defined by reciprocal cross-neutralization in vitro.

scholarly journals Development of a Coronavirus Disease 2019 Nonhuman Primate Model Using Airborne Exposure

2020 ◽  
Author(s):  
Sara C. Johnston ◽  
Alexandra Jay ◽  
Jo Lynne Raymond ◽  
Franco Rossi ◽  
Xiankun Zeng ◽  
...  
Keyword(s):  
Nonhuman Primate ◽  
Rhesus Macaques ◽  
Airborne Transmission ◽  
Primate Model ◽  
Viral Shedding ◽  
Airborne Exposure ◽  
Successful Infection ◽  
Cynomolgus Macaques ◽  
Virus Exposure ◽  
Green Monkeys

AbstractAirborne transmission is predicted to be a prevalent route of human exposure with SARS-CoV-2. Aside from African green monkeys, nonhuman primate models that replicate airborne transmission of SARS-CoV-2 have not been investigated. A comprehensive and comparative evaluation of COVID-19 in African green monkeys, rhesus macaques, and cynomolgus macaques following airborne exposure to SARS-CoV-2 was performed to define parameters critical to disease progression and the extent to which they correlate with human COVID-19. Respiratory abnormalities and viral shedding were noted for all animals, indicating successful infection. Cynomolgus macaques developed fever, and thrombocytopenia was measured for African green monkeys and rhesus macaques. Type II pneumocyte hyperplasia and alveolar fibrosis were more frequently observed in lung tissue from cynomolgus macaques and African green monkeys. The data indicate that, in addition to African green monkeys, macaques can be successfully infected by airborne SARS-CoV-2, providing viable macaque natural transmission models for medical countermeasure evaluation.One Sentence SummaryNonhuman primates develop COVID-19 following airborne virus exposure.

scholarly journals A recombinant receptor-binding domain in trimeric form generates completely protective immunity against SARS-CoV-2 infection in nonhuman primates

2021 ◽  
Author(s):  
Limin Yang ◽  
Deyu Tian ◽  
Jian-bao Han ◽  
Wenhui Fan ◽  
Yuan Zhang ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Nonhuman Primates ◽  
Rhesus Macaques ◽  
Vaccination Strategy ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Recombinant Receptor ◽  
High Level ◽  
Cellular Immune

Safe and effective vaccination is critical to combatting the COVID-19 pandemic. Here, we developed a trimeric SARS-CoV-2 receptor-binding domain (RBD) subunit vaccine candidate that simulates the natural structure of the spike (S) trimer glycoprotein. Immunization with RBD-trimer induced robust humoral and cellular immune responses and a high level of neutralizing antibodies that were maintained for at least 4 months. Moreover, the antibodies that were produced in response to the vaccine effectively neutralized the SARS-CoV-2 501Y.V2 variant. Of note, when the titers of the antibodies dropped to a sufficiently low level, only one boost quickly activated the anamnestic immune response, resulting in complete protection against the SARS-CoV-2 challenge in rhesus macaques without typical histopathological changes or viral replication in the lungs and other respiratory tissues. Our results indicated that immunization with SARS-CoV-2 RBD-trimer could raise long-term and broad immunity protection in nonhuman primates, thereby offering an optimal vaccination strategy against COVID-19.

scholarly journals Safety and Potency of COVIran Barekat Inactivated Vaccine Candidate for SARS-CoV-2: A Preclinical Study

2021 ◽  
Author(s):  
Asghar Abdoli ◽  
Reza Aalizadeh ◽  
Hossein Aminianfar
Keyword(s):  
Neutralizing Antibodies ◽  
Rhesus Macaques ◽  
Preclinical Study ◽  
Control Group ◽  
Potential Candidate ◽  
Global Pandemic ◽  
Efficient Protection ◽  
High Level ◽  
Different Doses ◽  
Potent Immune Response

There is an urgent demand to manufacture an effective and safe vaccine to prevent SARS-CoV2 infection, which resulted in a global pandemic. In this study, we developed an inactivated whole-virus SARS-CoV-2 candidate vaccine named COVIran Barekat. Immunization at two different doses (3 microgram or 5 microgram per dose) elicited a high level of SARS-CoV-2 specific neutralizing antibodies in mice, rabbits, and non-human primates. The results show the safety profile in studied animals (include guinea pig, rabbit, mice, and monkeys). Rhesus macaques were immunized with the two-dose of 5 microgram and microgram of the COVIran Barekat vaccine and showed highly efficient protection against 104 TCID50 of SARS-CoV-2 intratracheal challenge compared with the control group. These results highlight the COVIran Barekat vaccine as a potential candidate to induce a strong and potent immune response which may be a promising and feasible vaccine to protect against SARS-CoV2 infection.

scholarly journals A sand fly salivary protein vaccine shows efficacy against vector-transmitted cutaneous leishmaniasis in nonhuman primates

2015 ◽  
Vol 7 (290) ◽  
pp. 290ra90-290ra90 ◽  
Author(s):  
Fabiano Oliveira ◽  
Edgar Rowton ◽  
Hamide Aslan ◽  
Regis Gomes ◽  
Philip A. Castrovinci ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Nonhuman Primates ◽  
Mononuclear Cells ◽  
Rhesus Macaques ◽  
Parasite Burden ◽  
Salivary Protein ◽  
Sand Fly ◽  
Protein Vaccine ◽  
Peripheral Blood Mononuclear ◽  
Phlebotomus Duboscqi

Currently, there are no commercially available human vaccines against leishmaniasis. In rodents, cellular immunity to salivary proteins of sand fly vectors is associated to protection against leishmaniasis, making them worthy targets for further exploration as vaccines. We demonstrate that nonhuman primates (NHP) exposed to Phlebotomus duboscqi uninfected sand fly bites or immunized with salivary protein PdSP15 are protected against cutaneous leishmaniasis initiated by infected bites. Uninfected sand fly–exposed and 7 of 10 PdSP15-immunized rhesus macaques displayed a significant reduction in disease and parasite burden compared to controls. Protection correlated to the early appearance of Leishmania-specific CD4+IFN-γ+ lymphocytes, suggesting that immunity to saliva or PdSP15 augments the host immune response to the parasites while maintaining minimal pathology. Notably, the 30% unprotected PdSP15-immunized NHP developed neither immunity to PdSP15 nor an accelerated Leishmania-specific immunity. Sera and peripheral blood mononuclear cells from individuals naturally exposed to P. duboscqi bites recognized PdSP15, demonstrating its immunogenicity in humans. PdSP15 sequence and structure show no homology to mammalian proteins, further demonstrating its potential as a component of a vaccine for human leishmaniasis.

scholarly journals Toward a More Expansive Discourse in a Changing World: An Analysis of Political Leaders’ Speeches on Biodiversity

2021 ◽  
Vol 13 (5) ◽  
pp. 2899
Author(s):  
Sang Hun Lee ◽  
Yi Hyun Kang ◽  
Rong Dai
Keyword(s):  
Biodiversity Conservation ◽  
Policy Process ◽  
Biological Diversity ◽  
Convention On Biological Diversity ◽  
Decision Making Process ◽  
Political Leaders ◽  
Host Countries ◽  
Global Pandemic ◽  
The Subject ◽  
High Level

Speeches delivered in the Conference of the Parties (COPs) to the Convention on Biological Diversity represent leading discourses about biodiversity conservation. The discourse shared by high-level politicians is especially influential in the financing and decision-making process of global biodiversity governance. However, the speeches given in the COPs have not been the subject of systematic analyses until now. This study analyzes the host countries’ speeches given at the six most recent COPs and investigates which discourses have been expressed in the speeches. The regulatory discourse that views nature as a resource was found to be the dominant discourse, while other discourses that view nature as a scientific object or a spiritual entity were represented only marginally. As the need for a transformational policy for biodiversity conservation is growing amid a global pandemic, it is essential to deepen our understanding of the dynamics and complexity of nature and reflect it in the policy process. This study suggests that more balanced discourse on biodiversity may earn broader audiences’ consensus on biodiversity conservation.

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