scholarly journals Chimpanzees as an animal model for human norovirus infection and vaccine development

2010 ◽  
Vol 108 (1) ◽  
pp. 325-330 ◽  
Author(s):  
Karin Bok ◽  
Gabriel I. Parra ◽  
Tanaji Mitra ◽  
Eugenio Abente ◽  
Charlene K. Shaver ◽  
...  
Keyword(s):  
Animal Model ◽  
Vaccine Development ◽  
Control Strategies ◽  
Serum Antibody ◽  
Clinical Signs ◽  
Antigen Expression ◽  
Norwalk Virus ◽  
Human Norovirus ◽  
Virus Shedding ◽  
Model Studies

Noroviruses are global agents of acute gastroenteritis, but the development of control strategies has been hampered by the absence of a robust animal model. Studies in chimpanzees have played a key role in the characterization of several fastidious hepatitis viruses, and we investigated the feasibility of such studies for the noroviruses. Seronegative chimpanzees inoculated i.v. with the human norovirus strain Norwalk virus (NV) did not show clinical signs of gastroenteritis, but the onset and duration of virus shedding in stool and serum antibody responses were similar to that observed in humans. NV RNA was detected in intestinal and liver biopsies concurrent with the detection of viral shedding in stool, and NV antigen expression was observed in cells of the small intestinal lamina propria. Two infected chimpanzees rechallenged 4, 10, or 24 mo later with NV were resistant to reinfection, and the presence of NV-specific serum antibodies correlated with protection. We evaluated the immunogenicity and efficacy of virus-like particles (VLPs) derived from NV (genogroup I, GI) and MD145 (genogroup II, GII) noroviruses as vaccines. Chimpanzees vaccinated intramuscularly with GI VLPs were protected from NV infection when challenged 2 and 18 mo after vaccination, whereas chimpanzees that received GII VLPs vaccine or a placebo were not. This study establishes the chimpanzee as a viable animal model for the study of norovirus replication and immunity, and shows that NV VLP vaccines could induce protective homologous immunity even after extended periods of time.

scholarly journals A Sequential Study on the Pathology of Peste Des Petits Ruminants and Tissue Distribution of the Virus Following Experimental Infection of Black Bengal Goats

2021 ◽  
Vol 8 ◽  
Author(s):  
Shahana Begum ◽  
Mohammed Nooruzzaman ◽  
Mohammad Rafiqul Islam ◽  
Emdadul Haque Chowdhury
Keyword(s):  
Experimental Infection ◽  
Control Strategies ◽  
Clinical Signs ◽  
Electrolyte Imbalance ◽  
Effective Control ◽  
Peste Des Petits Ruminants ◽  
Virus Shedding ◽  
Liver And Kidney ◽  
Ulcerative Lesions ◽  
Lineage Iv

We studied the sequential pathology of peste des petits ruminants (PPR) in Black Bengal goats and analyzed virus distribution in tissues and virus shedding following experimental infection with a Bangladeshi isolate of lineage IV PPR virus (PPRV). The early clinical signs like fever, depression, and ocular and nasal discharges first appeared at 4–7 days post-infection (dpi). Three out of eight inoculated goats died at 13, 15, and 18 dpi, and the rest were killed at different time points from 5 to 18 dpi. Initially, the virus multiplied mostly in the lymphoid organs of the pharyngeal region and caused extensive lymphoid destruction and hemorrhages. This was followed by viremia, massive virus replication in the lungs, and pneumonia along with the appearance of the clinical signs. Subsequently, the virus spread to other organs causing necrotic and hemorrhagic lesions, as well as the virus localized in the upper respiratory, oral and intestinal mucosa resulting in catarrhal, erosive, and ulcerative lesions. On hematological and biochemical investigation progressive leukopenia and hypoproteinemia, a gradual increase of serum metabolites and enzymes associated with liver and kidney damage, and electrolyte imbalance were observed. Seroconversion started at 7 dpi and all the surviving animals had serum antibodies at 14 dpi. Virus shedding was observed in nasal and ocular secretions at 4 dpi and in feces and urine at 14 dpi, which gradually increased and continued till the end of the experiment (18 dpi) despite seroconversion. Therefore, the virus shedding of naturally infected seroconverted goats should be monitored for effective control strategies.

scholarly journals Mammalian animal models for dengue virus infection: a recent overview

2021 ◽  
Author(s):  
Mohammad Enamul Hoque Kayesh ◽  
Kyoko Tsukiyama-Kohara
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Dengue Virus ◽  
Dengue Fever ◽  
Vaccine Development ◽  
Wide Spectrum ◽  
Tree Shrew ◽  
Clinical Signs ◽  
Denv Infection ◽  
Health Concern

AbstractDengue, a rapidly spreading mosquito-borne human viral disease caused by dengue virus (DENV), is a public health concern in tropical and subtropical areas due to its expanding geographical range. DENV can cause a wide spectrum of illnesses in humans, ranging from asymptomatic infection or mild dengue fever (DF) to life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Dengue is caused by four DENV serotypes; however, dengue pathogenesis is complex and poorly understood. Establishing a useful animal model that can exhibit dengue-fever-like signs similar to those in humans is essential to improve our understanding of the host response and pathogenesis of DENV. Although several animal models, including mouse models, non-human primate models, and a recently reported tree shrew model, have been investigated for DENV infection, animal models with clinical signs that are similar to those of DF in humans have not yet been established. Although animal models are essential for understanding the pathogenesis of DENV infection and for drug and vaccine development, each animal model has its own strengths and limitations. Therefore, in this review, we provide a recent overview of animal models for DENV infection and pathogenesis, focusing on studies of the antibody-dependent enhancement (ADE) effect in animal models.

scholarly journals ChAdOx1 nCoV-19 protection against SARS-CoV-2 in rhesus macaque and ferret challenge models

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Teresa Lambe ◽  
Alexandra J. Spencer ◽  
Kelly M. Thomas ◽  
Karen E. Gooch ◽  
Stephen Thomas ◽  
...  
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Vaccine Development ◽  
Rhesus Macaques ◽  
Antibody Responses ◽  
High Dose ◽  
Lung Pathology ◽  
Virus Shedding ◽  
Immune Profiling ◽  
Careful Assessment

AbstractVaccines against SARS-CoV-2 are urgently required, but early development of vaccines against SARS-CoV-1 resulted in enhanced disease after vaccination. Careful assessment of this phenomena is warranted for vaccine development against SARS CoV-2. Here we report detailed immune profiling after ChAdOx1 nCoV-19 (AZD1222) and subsequent high dose challenge in two animal models of SARS-CoV-2 mediated disease. We demonstrate in rhesus macaques the lung pathology caused by SARS-CoV-2 mediated pneumonia is reduced by prior vaccination with ChAdOx1 nCoV-19 which induced neutralising antibody responses after a single intramuscular administration. In a second animal model, ferrets, ChAdOx1 nCoV-19 reduced both virus shedding and lung pathology. Antibody titre were boosted by a second dose. Data from these challenge models on the absence of enhanced disease and the detailed immune profiling, support the continued clinical evaluation of ChAdOx1 nCoV-19.

scholarly journals Identification of HIV-1 Envelope Mutations that Enhance Entry Using Macaque CD4 and CCR5

2019 ◽  
Author(s):  
Jeremy I. Roop ◽  
Noah A. Cassidy ◽  
Adam S. Dingens ◽  
Jesse D. Bloom ◽  
Julie Overbaugh
Keyword(s):  
Animal Model ◽  
Neutralizing Antibodies ◽  
Bound States ◽  
Vaccine Development ◽  
Rhesus Macaques ◽  
Heptad Repeat ◽  
Design Strategies ◽  
Model Studies ◽  
Macaque Model ◽  
Hiv 1

AbstractAlthough Rhesus macaques are an important animal model for HIV-1 vaccine development research, most transmitted HIV-1 strains replicate poorly in macaque cells. A major genetic determinant of this species-specific restriction is a non-synonymous mutation in macaque CD4 that results in reduced HIV-1 Envelope (Env)-mediated viral entry compared to human CD4. Recent research efforts employing either laboratory evolution or structure-guided design strategies have uncovered several mutations in Env’s gp120 subunit that enhance binding of macaque CD4 by transmitted/founder HIV-1 viruses. In order to identify additional Env mutations that promote infection of macaque cells, we utilized deep mutational scanning to screen thousands of Env point mutants for those that enhance HIV-1 entry via macaque receptors. We identified many uncharacterized amino acid mutations in the N-terminal heptad repeat (NHR) and C-terminal heptad repeat (CHR) regions of gp41 that increased entry into cells bearing macaque receptors by up to 38-fold. Many of these mutations also modestly increased infection of cells bearing human CD4 and CCR5 (up to 13-fold). NHR/CHR mutations identified by deep mutational scanning that enhanced entry also increased sensitivity to neutralizing antibodies targeting the MPER epitope, and to inactivation by cold-incubation, suggesting that they promote sampling of an intermediate trimer conformation between closed and receptor bound states. Identification of this set of mutations can inform future macaque model studies, and also further our understanding of the relationship between Env structure and function.ImportanceAlthough Rhesus macaques are the favored non-human primate animal model used in HIV-1 research, most circulating HIV-1 strains poorly infect macaque cells. Studies using macaques to model HIV-1 infection often use evolved, or mutant HIV-1 variants that are able to utilize macaque CD4, but these HIV-1 variants poorly model infection by circulating strains. In this work, we sought to identity HIV-1 mutations that would allow entry into macaque cells, but that would maintain critical characteristics of circulating HIV-1 strains. We employed a powerful experimental method to simultaneously assess the effects of thousands of individual HIV-1 mutations on infection of cells bearing macaque receptors. We identified many previously uncharacterized mutations that enhance infection of circulating HIV-1 strains into cells bearing macaque receptors by up to 38-fold. Identification of these mutations may be of use in future macaque model studies.

scholarly journals Susceptibility of raccoon dogs for experimental SARS-CoV-2 infection

2020 ◽  
Author(s):  
Conrad M. Freuling ◽  
Angele Breithaupt ◽  
Thomas Müller ◽  
Julia Sehl ◽  
Anne Balkema-Buschmann ◽  
...  
Keyword(s):  
Intermediate Host ◽  
Risk Mitigation ◽  
Control Strategies ◽  
Clinical Signs ◽  
Mitigation Strategies ◽  
Nyctereutes Procyonoides ◽  
Intermediate Hosts ◽  
Virus Shedding ◽  
High Level ◽  
Raccoon Dogs

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China at the end of 2019, and became pandemic. The zoonotic virus most likely originated from bats, but definite intermediate hosts have not yet been identified. Raccoon dogs (Nyctereutes procyonoides) are kept for fur production, in particular in China, and were suspected as potential intermediate host for both SARS-CoV6 and SARS-CoV2. Here we demonstrate susceptibility of raccoon dogs for SARS-CoV-2 infection after intranasal inoculation and transmission to direct contact animals. Rapid, high level virus shedding, in combination with minor clinical signs and pathohistological changes, seroconversion and absence of viral adaptation highlight the role of raccoon dogs as a potential intermediate host. The results are highly relevant for control strategies and emphasize the risk that raccoon dogs may represent a potential SARS-CoV-2 reservoir. Our results support the establishment of adequate surveillance and risk mitigation strategies for kept and wild raccoon dogs.Article Summary LineRaccoon dogs are susceptible to and efficiently transmit SARS-CoV2 and may serve as intermediate host

scholarly journals Comparison of Human-Like H1 (-Cluster) Influenza A Viruses in the Swine Host

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Janice R. Ciacci Zanella ◽  
Amy L. Vincent ◽  
Eraldo L. Zanella ◽  
Alessio Lorusso ◽  
Crystal L. Loving ◽  
...  
Keyword(s):  
Respiratory Disease ◽  
Lower Respiratory Tract ◽  
Influenza A ◽  
Control Strategies ◽  
Serum Antibody ◽  
Clinical Signs ◽  
Cross Reactivity ◽  
Influenza Viruses ◽  
Influenza A Viruses ◽  
Antibody Titers

Influenza A viruses cause acute respiratory disease in swine. Viruses with H1 hemagglutinin genes from the human seasonal lineage (-cluster) have been isolated from North American swine since 2003. The objective of this work was to study the pathogenesis and transmission of -cluster H1 influenza viruses in swine, comparing three isolates from different phylogenetic subclusters, geographic locations, and years of isolation. Two isolates from the 2 subcluster, A/sw/MN/07002083/07 H1N1 (MN07) and A/sw/IL/00685/05 H1N1 (IL05), and A/sw/TX/01976/08 H1N2 (TX08) from the 1 sub-cluster were evaluated. All isolates caused disease and were transmitted to contact pigs. Respiratory disease was apparent in pigs infected with MN07 and IL05 viruses; however, clinical signs and lung lesions were reduced in severity as compared to TX08. On day 5 following infection MN07-infected pigs had lower virus titers than the TX08 pigs, suggesting that although this H1N1 was successfully transmitted, it may not replicate as efficiently in the upper or lower respiratory tract. MN07 and IL05 H1N1 induced higher serum antibody titers than TX08. Greater serological cross-reactivity was observed for viruses from the same HA phylogenetic sub-cluster; however, antigenic differences between the sub-clusters may have implications for disease control strategies for pigs.

scholarly journals Assessment of the ferret as an in vivo model for mumps virus infection

2013 ◽  
Vol 94 (6) ◽  
pp. 1200-1205 ◽  
Author(s):  
L. Parker ◽  
S. M. Gilliland ◽  
P. Minor ◽  
S. Schepelmann
Keyword(s):  
Animal Model ◽  
Cytokine Production ◽  
Serum Antibody ◽  
Clinical Signs ◽  
Mumps Virus ◽  
In Vivo Model ◽  
Live Virus ◽  
Suitable Animal Model ◽  
Tissue Homogenates

Humans are the sole reservoir for mumps virus (MuV), the causative agent of mumps. No animal model currently exists; therefore, in vivo knowledge of the virus is limited. Ferrets were assessed for their susceptibility to MuV based on their success as a model for influenza. We infected ferrets with clinical or attenuated vaccine MuVs by the nasal route and demonstrated evidence of immunogenicity in these animals with generation of a serum antibody response specific to MuV infection and cytokine production consistent with infection. However, no live virus or viral RNA was detected in nasal washes, oral swabs, urine, faeces or tissue homogenates, and no animals exhibited clinical signs. We suggest results to be obtained from ferrets are limited in fundamental in vivo MuV research and that they may not be a suitable animal model for this virus.

“In vitro” and in Animal Model Studies on a Double Virus- Inactivated Factor VIII Concentrate

1995 ◽  
Vol 74 (03) ◽  
pp. 868-873 ◽  
Author(s):  
Silvana Arrighi ◽  
Roberta Rossi ◽  
Maria Giuseppina Borri ◽  
Vladimir Lesnikov ◽  
Marina Lesnikov ◽  
...  
Keyword(s):  
Heat Treatment ◽  
Animal Model ◽  
Factor Viii ◽  
Hepatitis A ◽  
Hepatitis A Virus ◽  
Virus Inactivation ◽  
Enveloped Viruses ◽  
Model Studies ◽  
Heat Treated

SummaryTo improve the safety of plasma derived factor VIII (FVIII) concentrate, we introduced a final super heat treatment (100° C for 30 min) as additional virus inactivation step applied to a lyophilized, highly purified FVIII concentrate (100 IU/mg of proteins) already virus inactivated using the solvent/detergent (SID) method during the manufacturing process.The efficiency of the super heat treatment was demonstrated in inactivating two non-lipid enveloped viruses (Hepatitis A virus and Poliovirus 1). The loss of FVIII procoagulant activity during the super heat treatment was of about 15%, estimated both by clotting and chromogenic assays. No substantial changes were observed in physical, biochemical and immunological characteristics of the heat treated FVIII concentrate in comparison with those of the FVIII before heat treatment.

scholarly journals Protection against the New Equine Influenza Virus Florida Clade I Outbreak Strain Provided by a Whole Inactivated Virus Vaccine

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 784
Author(s):  
Sylvia Reemers ◽  
Sander van Bommel ◽  
Qi Cao ◽  
David Sutton ◽  
Saskia van de Zande
Keyword(s):  
Influenza Virus ◽  
Virus Vaccine ◽  
Clinical Signs ◽  
Field Strain ◽  
Equine Influenza Virus ◽  
Outbreak Strain ◽  
Virus Shedding ◽  
Equine Influenza ◽  
Vaccine Type ◽  
High Level

Equine influenza virus (EIV) is a major cause of respiratory disease in horses. Vaccination is an effective tool for infection control. Although various EIV vaccines are widely available, major outbreaks occurred in Europe in 2018 involving a new EIV H3N8 FC1 strain. In France, it was reported that both unvaccinated and vaccinated horses were affected despite >80% vaccination coverage and most horses being vaccinated with a vaccine expressing FC1 antigen. This study assessed whether vaccine type, next to antigenic difference between vaccine and field strain, plays a role. Horses were vaccinated with an ISCOMatrix-adjuvanted, whole inactivated virus vaccine (Equilis Prequenza) and experimentally infected with the new FC1 outbreak strain. Serology (HI), clinical signs, and virus shedding were evaluated in vaccinated compared to unvaccinated horses. Results showed a significant reduction in clinical signs and a lack of virus shedding in vaccinated horses compared to unvaccinated controls. From these results, it can be concluded that Equilis Prequenza provides a high level of protection to challenge with the new FC1 outbreak strain. This suggests that, apart from antigenic differences between vaccine and field strain, other aspects of the vaccine may also play an important role in determining field efficacy.

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