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Center of Excellence for Emerging and Zoonotic Animal Diseases

BSL-3 trainingJordan field studies

CEEZAD

1800 Denison Ave
Mosier Hall, Room P200
Manhattan, KS  66506

785-532-2793   
785-532-3373 fax
CEEZAD@ksu.edu

 The Center of Excellence for Emerging and Zoonotic Animal Diseases (CEEZAD) at Kansas State University was established in 2010 to help protect the nation’s agricultural and public health sectors against a high-consequence foreign animal, emerging and zoonotic disease threats. CEEZAD has four principal missions:

  • Development of novel, safe, efficacious, and DIVA-compatible vaccines for prevention and control of high-impact emerging and zoonotic diseases that can be manufactured in the U.S.
  • Development and expansion of technologies and platforms for laboratory and point-of-need pathogen detection.
  • Development of models to predict high-consequence disease behavior in the U.S. to aid prevention or outbreak control.
  • Development of education and training programs for students, veterinarians, first responders, and researchers in high-impact animal diseases and animal emergencies.

 News/Events Highlights

July 17, 2022

New study finds that certain SARS-CoV-2 Spike mutations are important for infection of mice but not for escape from human immune sera

A recently published article co-authored by the director of the Center of Excellence for Emerging and Zoonotic Animal Diseases (www.ceezad.org) and the Center on Emerging and Zoontic Infectious Diseases (https://www.k-state.edu/cezid) reports on new findings dealing with infection of mice with  SARS CoV-2.

The article was published in the July edition of the journal Nature Communications. Dr. Juergen A. Richt, Regents Distinguished Professor at Kansas State University and director of CEEZAD and CEZID, was among the authors.

David A. Meekins, Chester D. McDowell and Velmurugan Belaraman, all members of the CEEZAD research team, were also among co-authors.

Due to differences in the human and murine angiotensin converting enzyme 2 (ACE-2) receptor, initially circulating, ancestral Wuhan-like  SARS-CoV-2 isolates could not infect mice. But in the article, the authors demonstrate that serial passaging of the Wuhan-like USA-WA1/2020 SARS-Cov-2 strain in mice  results in a "mouse-adapted" SARS-CoV-2 strain (MA-SARS-CoV-2) with mutations in S, M, and N genes, and a twelve-nucleotide insertion in the S gene.

They also found that MA-SARS-CoV-2 infection in mice causes mild disease, with more pronounced morbidity depending on genetic background and in aged and obese animals. Two mutations in the S gene associated with the mouse adaptation (N501Y, H655Y) are also present in various SARS-CoV-2 variants of concern (VoCs).

The N501Y substitution in the receptor binding domain present also in  Alpha, Beta, Gamma and Omicron VoCs,  is associated with high transmissibility in humans and allows these VoCs to infect wild type mice. The authors also found that the S protein mutations found in the mouse-adapted  MA-SARS-CoV-2 strain do not affect neutralization efficiency by human convalescent and post vaccination sera.

The full article can be read by following this link. Characterization of SARS-CoV-2 Spike mutations important for infection of mice and escape from human immune sera - PubMed (nih.gov)

July 15, 2022

Article reports on the development of indirect ELISAs for the detection of SARS CoV-2 antibodies in cats

A recently published article reports on findings by members of the Center of Excellence for Emerging and Zoonotic Animal Diseases (www.ceezad.org) leading to development of an indirect ELISA for the detection of SARS-CoV-2 antibodies in cats.

The article was published in the June edition of the journal Frontiers of Veterinary Science. Dr. Juergen A. Richt, Regents Distinguished Professor at Kansas State University and director of CEEZAD, was the senior author.

Co-authors were Dashzeveg Bold, Gleyder Roman-Sosa and Natasha Gaudreault, all associated with CEEZAD, as well as Roman Pogranichniy of the College of Veterinary Medicine at Kansas State University and Batsukh Zayat, of the Mongolian University of Life Sciences in Ulaanbaatar, Mongolia.

The article noted that companion animals such as cats are susceptible to a variety of coronaviruses, and recent studies show that felines are highly susceptible to SARS-CoV-2 infection.

RT-PCR diagnostic is currently the method of choice to detect the presence of SARS-CoV-2-specific viral nucleic acids in animal samples during an active infection; however, serological assays are critical to determine whether animals were exposed to the virus and to determine the seroprevalence of SARS-CoV-2 in a defined population.

In this study,  CEEZAD researchers utilized recombinant nucleocapsid (N) protein and the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 expressed in E. coli (N) and mammalian cells (N, RBD) to develop indirect Enzyme-linked Immunoassays s (iELISAs) using well-characterized SARS-CoV-2-positive and -negative cat serum panels from previous experimental cat challenge studies.

The optimal conditions for the iELISA tests were established based on checkerboard dilutions of antigens and antibodies. The diagnostic sensitivity for the detection of feline antibodies specific for the SARS-CoV-2 N or RBD proteins of the iELISA tests was between 93.3 and 97.8%, respectively, and the diagnostic specificity 95.5%.

The iELISAs developed here can be used for high-throughput screening of cat sera for both SARS-CoV-2-specific antigens. The testing  of SARS-CoV-2-specific antibodies with the iELISAs can be performed in a BSL-2 biocontainment environment, unlike classical virus neutralization tests with live virus which have to be performed in BSL-3 laboratories.

 

BSL-3 Training/Transboundary Animal Diseases Summer Program
June 5-16, 2022

BSL-3 Agenda

 

June 2, 2022

Ten students selected for CEEZAD’s 2022 BSL-3 Summer Training Program

An upcoming CEEZAD summer workshop will give 10 future veterinary researchers a chance to explore the full range of professional opportunities that will be available to them when they complete their studies. It will also acquaint those candidates with recent developments in the field of infectious disease studies in BSL-3 biocontainment.

The USDA BSL-3 Training Program for Research Support Personnel is an annual exercise in which CEEZAD gathers experts in the fields of biosecurity, virology, pathobiology and related fields in order to educate promising candidates who are interested in veterinary research in those fields. It will be held from June 5-17. Most of the sessions will take place at the Biosecurity Research Institute, a level 3 biocontainment facility at Kansas State University.

The program is funded by the United States Department of Agriculture-Agricultural Research Service.

The participants, most of them PhD candidates, are involved in the study of various infectious diseases. Here are brief biographies along with descriptions of their future aspirations:

Wellesley Dittmar. A veterinary medicine and PhD student at Louisiana State University, Wellesley received her bachelors in biological engineering from Mississippi State in 2020. Wellesley has conducted research at the Department of Agricultural and Biological Engineering at Mississippi State, including the design of a device to measure blood flow within a laminitic equine hoof.

Her career goal is to become either a faculty member at a veterinary school or to pursue research at the Centers For Disease Control in order to identify and investigate new viruses in hot spots around the world.

Astrid Carcamo-Tzic. Astrid is a veterinary medicine technician at Kansas State University with an expected graduation date of 2026. Holder of bachelors and masters degrees from Kansas State, she is also a study assistant in clinical operations at Dechra Veterinary Products in Overland Park, Ks.

Astrid hopes to use the experience acquired through the CEEZAD BSL3 Summer Program to enhance her understanding of high-risk pathogens, among them African Swine Fever and Rift Valley Fever virus, and biosafety.

Emily Hedden. Holder of bachelors and masters degrees, the latter in veterinary biomedical science, from Kansas State University, Emily is working on a USDA-ARS arbovirology fellowship at the Oak Ridge Institute For Science and Education.

She wants to use the CEEZAD summer program to enhance her understanding of the process and importance of collaborations within industry, academia and the government that are required to help reduce the consequences of zoonotic animal diseases on public health.

Shelby Cagle. A PhD student in microbiology, immunology and pathology at Colorado State, Shelby holds a bachelors degree from the University of Tennessee in science communication and microbiology. She is a graduate research assistant at the Colorado State Center for Vector-Borne Infectious Diseases.

Shelby believes the CEEZAD summer program will provide the hands-on training needed for the safe conduct of BSL-3 level experiments, which will be the hallmark of her PhD work and future career aspirations.

Albert To. Holder of a PhD in biomedical sciences from the University of Hawaii at Manoa, Albert is a post-doctoral researcher in the Department of Tropical Medicine at the University of Hawaii.

Albert hopes to develop diagnostic antigen tests and preventative countermeasures for emerging pathogens, especially from regions that lack the technological capacity and/or workforce to do so. He hopes to use his knowledge gained during the CEEZAD summer program to advance that goal.

Zachary Baker. Zach is a graduate student working toward a PhD in molecular and cellular biology at Virginia Tech, where he received his bachelors in 2020. He is also working at the Hsu Lab at Virginia Tech.

Zach believes the CEEZAD summer program will enhance his ability to deal with potentially deadly pathogens that can infect the gastrointestinal tract, particularly those he may research as a professional in the field.

Emily Bencosme-Cuevas. A PhD student in veterinary pathobiology at Texas A&M’s College of Veterinary Medicine and Biomedical Sciences, Emily has a bachelors degree from Northwestern State University in Louisiana.

Emily believes that the CEEZAD summer program will complement her graduate training to advance a long-term goal of becoming a primary investigator in the field of vaccine research against zoonotic diseases, including some that are studied under high-containment conditions. Emily also looks forward to the opportunity to interact with various industry experts.

Marina Wylie. Marina is a PhD candidate in the Emerging Infectious Diseases graduate program of the Uniformed Services University of the Health Sciences.

Marina holds a bachelors degree from the College of Arts and Sciences at the University of Miami, and has worked as a lab assistant at the University of Miami. Her goal is to use the CEEZAD summer program as a means of determining whether her future interests will focus on BSL3/4 animal research.

Viktoria Van Nederveen. Viktoria is a PhD candidate in the Emerging Infectious Diseases program at the Uniformed Services University of the Health Sciences. Viktoria holds a bachelors degree in biochemistry and molecular biology from Lebanon Valley College.

Emily Medina Magues. Emily is a master of science student at the University of Wisconsin-Madison, where she is studying comparative biomedical sciences. Emily holds a degree in molecular biology from Wisconsin, and is interested in studying human and animal immunology and virology.

Emily hopes to use the CEEZAD summer program to advance her goal of working in high-containment environments. Emily also expects to learn much from hearing from industry and government leaders as well as research experts working in the field of high-containment and trans-boundary diseases.

 

 

May 26, 2022

KSU honors CEEZAD director, two staffers, for patent work

The director of the Center of Excellence For Emerging and Zoonotic Animal Diseases (CEEZAD, www.ceezad.org) was among Kansas State University faculty members honored May 9 for patents on discoveries made during 2021.

Dr. Juergen A. Richt, the Regents and University Distinguished Professor at K-State, was one of three CEEZAD researchers honored during the university’s Inventors and breeders Ceremony. The event recognized faculty members who were issued patents and plant variety protection certificates in 2021.

Also honored from CEEZAD were Dr. Igor Morozov, science project manager, and Sun Young Sunwoo, who at the time was a researcher affiliated with CEEZAD and the Richt Lab.

All three were honored for their work leading to a patent regarding the development of a vaccine to prevent Epizootic Hemorrhagic Disease. That is a disease of white-tailed deer and cattle transmitted by midges.

May 13, 2022

CEEZAD receives NIHr01 grant to study infectious diseases

The National Institute of Health (NIH) has awarded a more than $3.7 million grant to the Center of Excellence for Emerging and Zoonotic Animal Diseases (CEEZAD, www.ceezad.org) for research related to the study of influenza in humans.

NIH r01 grants provide support for health-related research and development. The award is made in conjunction with researchers at the University of Missouri. The two teams of researchers will be working cooperatively.

The research will focus on the ability of genetically modified pigs to model NKT cell immunity to infection with influenza viruses.

Pulmonary T cell-mediated immunity is critical for host protection from influenza virus infections. While current understanding of influenza immunity is focused on conventional MHC-restricted T cells that recognize peptide antigens, unconventional innate-like T cell subsets such as CD1d-restricted invariant natural killer T (NKT) cells, are emerging as integral effector components of the respiratory immune system, where they can play both a protective and immuno-pathological role in respiratory infections.

Although NKT cells are thought to make important contributions to influenza immunity, relatively little is known about their impact on human influenza infections due to a lack of suitable animal models.

The current proposal seeks to address this critical knowledge gap using swine, which offer an excellent model to determine the role of NKT cells for human influenza infections, including anti-influenza host defenses and influenza vaccine responses.

The award was made through the National Institute of Allergy and Infectious Diseases.

 

April 29, 2022

New paper examines transmission patterns of mutations in SARS-CoV-2 variants

The Director of the Center of Excellence For Emerging and Zoonotic Animal Diseases (CEEZAD; www.ceezad.org) and the Center on Emerging and Zoonotic Infectious Diseases (www.k-state.erdu/cezid) is co- author of a recently published paper examining transmission patterns of various mutations of the SARS-CoV-2 virus.

The paper, by Dr. Juergen A. Richt, who in addition to his duties at CEEZAD and CEZID is also the Regents and University Distinguished Professor at Kansas State University, and other CEEZAD-affiliated researchers, was published in the March edition of Cell Host and Microbe, an offshoot of Cell Press.  

SARS-CoV-2 has diverged into different variants termed "variants of concern" (VOCs). In the paper, researchers examined emerging SARS-CoV-2 spike polymorphisms in vitro and in vivo to understand their impact on transmissibility, virus pathogenicity and fitness. They found that the substitution Spike655Y, represented in the gamma and omicron VOCs, enhances viral replication and spike protein cleavage.

The Spike655Y substitution was transmitted more efficiently than its ancestor Spike655H in the hamster infection model and was able to outcompete Spike655H in the hamster model and in a human primary airway system.

They also analyzed a set of emerging SARS-CoV-2 variants of concern (VOCs) to investigate how different sets of mutations may impact spike processing. All VOCs tested exhibited increased spike cleavage and fusogenic capacity.

Taken together, the study demonstrates that the spike mutations present in VOCs that become epidemiologically prevalent in humans are linked to an increase in spike processing capabilities and virus transmission.

Co-authors, in addition to Dr. Richt, from CEEZAD and Richt Lab, included: David Meekins, Velmurugan Balaraman, and Chester McDowell.

The full study can be read by following this link: Mutations in SARS-CoV-2 variants of concern link to increased spike cleavage and virus transmission - PubMed (nih.gov)