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Center of Excellence for Emerging and Zoonotic Animal Diseases

News and Events Highlights

CEEZAD is a public source for the latest information on developments related to high-consequence foreign animal, emerging and zoonotic disease threats.

February 9, 2025

Article explores dynamics of H5N1 clade 2.3.4.4b infection in calves and cows

An 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 Zoonotic Infectious Diseases CEZID examines the dynamics of the spread of H5N1 clade 2.3.4.4b in experimentally infected calves and cows.

The article was co-authored by Dr. Juergen A. Richt, Regents and University Distinguished Professor at Kansas State University and director of CEEZAD and CEZID. Other co-authors include Konner Cool, Jessie D. Trujillo, Taeyong Kwon, Chester D. McDowell, Gagandeep Singh, Sujan Kafle, Natasha N. Gaudreault, and Igor Morozov, all of CEEZAD.

It was published in the January 2025 edition of the journal Nature.

In March 2024, highly pathogenic avian influenza virus (HPAIV) clade 2.3.4.4b H5N1 infections were reported in dairy cows in Texas. Rapid dissemination to more than 900  farms in 15 states followed. In this study researchers provide results of two independent clade 2.3.4.4b experimental infection studies evaluating the oronasal susceptibility to and transmission of a US H5N1 bovine isolate, genotype B3.13 (H5N1 B3.13), in calves, and the susceptibility of lactating cows following direct mammary gland inoculation of either H5N1 B3.13 or a current EU H5N1 wild bird isolate, genotype euDG (H5N1 euDG).

Inoculation of the calves resulted in moderate nasal replication and shedding with no severe clinical signs or transmission to sentinel calves. In dairy cows, infection resulted in no nasal shedding, but severe acute infection of the mammary gland with necrotizing mastitis and high fever, observed for both H5N1 isolates. Milk production was rapidly and markedly reduced and the physical condition of the cows was severely compromised.

Virus titers in milk rapidly peaked at 109 50% tissue culture infectious dose (TCID50) per ml, but systemic infection did not ensue. Notably, the adaptive mutation E627K emerged in the viral polymerase basic protein 2 (PB2) after intramammary replication of wild bird H5N1 isolate.

The research data suggests that in addition to H5N1 B3.13, other HPAIV H5N1 strains have the potential to replicate in the udder of cows and that milk and milking procedures, rather than respiratory spread, are likely to be the primary routes of H5N1 transmission between cattle.

The full article can be read by following this link: https://pubmed.ncbi.nlm.nih.gov/39321846/#:~:text=Nature,2024%20Sep%2025

February 5, 2025

CEEZAD study finds that pigs can transmit Mpox to sentinel animals

An article co-authored by 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 (CEZID; https://www.k-state.edu/cezid/) reports on findings concerning the transmission and susceptibility of the Mpox virus in a domestic livestock species.

The article was co-authored by Dr. Juergen A. Richt, Regents and University Distinguished Professor at Kansas State University and director of CEEZAD and CEZID. It was published in the December 13 edition of Emerging Microbes And Infections.

Other co-authors include Igor Morozov, Natasha N Gaudreault, Jessie D Trujillo, Konner Cool, Taeyong Kwon, Dashzeveg Bold, Velmurugan Balaraman, Patricia Assato, Emily Mantlo, Jayme Souza-Neto, Franco Matias Ferreyra, Jaime Retallick, Roman Pogranichniy, David A Meekins, Velmurugan Balaraman, Bianca Libanori Artiaga, Daniel W Madden and Chester McDowell, all of the Department of Diagnostic Medicine and Pathobiology at Kansas State University and CEEZAD.

Mpox virus (MPXV) is a re-emerging zoonotic poxvirus responsible for producing skin lesions in humans. Endemic in sub-Saharan Africa, the 2022 outbreak with a clade IIb strain has resulted in ongoing sustained transmission of the virus worldwide. MPXV has a relatively wide host range, with infections reported in rodent and non-human primate species. However, the susceptibility of many domestic livestock species remains unknown.

CEEZAD scientists conducted a susceptibility/transmission study in domestic pigs that were experimentally inoculated with a 2022 MPXV clade IIb isolate or served as sentinel contact control animals. Several principal-infected and sentinel contact control pigs developed minor lesions near the lips and nose starting at 12 through 18 days post-challenge (DPC). No virus was isolated and no viral DNA was detected from the lesions; however, MPXV antigen was detected by IHC in tissue from a pustule of a principal infected pig.

Viral DNA and infectious virus were detected in nasal and oral swabs up to 14 DPC, with peak titers observed at 7 DPC. Viral DNA was also detected in nasal tissues or skin collected from two principal-infected animals at 7 DPC post-mortem. Furthermore, all principal-infected and sentinel control animals enrolled in the study seroconverted.

The study provides the first evidence that domestic pigs are susceptible to experimental MPXV clade IIb infection and can transmit the virus to contact animals.

 

CEEZAD study explores immune responses against SARS-CoV-2 in bison, elk and other captive wildlife species

An article co-authored by 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 (CEZID; https://www.k-state.edu/cezid/) examines immune responses against the SARS-CoV-2 virus in bison, elk and other captive wildlife species.

The article was co-authored by Dr. Juergen A. Richt, Regents and University Distinguished Professor at Kansas State University and director of CEEZAD and CEZID. It was published in the September edition of Animals.

Other co-authors include Igor Morozov, Natasha N Gaudreault,  Roman Podgranichniy, Dashzeveg Bold, Mehrnaz Ardalan, and Konner Cool, all of the Department of Diagnostic Medicine and Pathobiology at Kansas State University and CEEZAD.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, has been found to infect various domestic and wild animal species. In this study, CEEZAD scientists collected and analyzed serum samples from 575 bison, 180 elk, and 147 samples from various wildlife species collected between 2020 and 2023 from several regions in the United States for the presence of SARS-CoV-2-specific antibodies.

Two commercial ELISA assays, one based on the inhibition of the SARS-CoV-2 receptor-binding domain (sVNT), the other on the detection of the nucleocapsid protein (N-ELISA) of SARS-CoV-2, were used. Positive samples from the sVNT were additionally evaluated using a conventional virus neutralization test (VNT). Our results indicated that 1.2% of bison, 2.2% of elk, and 4.1% of the other wildlife species serum samples were seropositive in the sVNT, whereas 4.2% of bison, 3.3% of elk, and 1.4% of the other captive wildlife species serum samples tested positive by the N-ELISA.

Among the sVNT serum samples, two samples from bison, one sample from elk, and five serum samples from other wildlife species (one cheetah, one gorilla, two lions, and one hippopotamus) had neutralizing antibody titers in the VNT, indicating these species are susceptible to SARS-CoV-2 infection.

These findings highlight the importance of broad surveillance efforts for the effective monitoring of SARS-CoV-2 in non-human hosts.

CEEZAD study finds Use of the Invariant Natural Killer T Cell Agonist α-Galactosylceramide as Adjuvant Can Lead to Vaccine-Associated Enhanced Respiratory Disease in Influenza-Vaccinated Pigs

An article co-authored by 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 (CEZID; https://www.k-state.edu/cezid/) discusses findings of  recent research linking a Natural Killer T (NKT) cell agonist to enhanced respiratory disease in influenza-vaccinated pigs.

The article was co-authored by Dr. Juergen A. Richt, Regents and University Distinguished Professor at Kansas State University and director of CEEZAD and CEZID. It was published in the September issue of Vaccines.

Other co-authors include Igor Morozov,  Taeyong Kwon, Dashzeveg Bold, Velmurugan Balaraman,  Bianca Libanori Artiaga, Jamie Henningson, Cassidy Keating, Daniel Madden and Chester McDowell, all of the Department of Diagnostic Medicine and Pathobiology at Kansas State University and CEEZAD.

Invariant natural killer T (iNKT) cells are glycolipid-reactive T cells with potent immunoregulatory properties. iNKT cells activated with the marine-sponge-derived glycolipid, α-galactosylceramide (αGC), are able to provide T cell help that has shown considerable promise for a wide array of therapeutic applications. This includes harnessing iNKT-cell-mediated immune responses to adjuvant whole inactivated influenza virus (WIV) vaccines.

An important concern with WIV vaccines is that under certain circumstances, they are capable of triggering vaccine-associated enhanced respiratory disease (VAERD) in influenza virus infected swine. This immunopathological phenomenon can arise after immunization with an oil-in-water (OIW) adjuvanted WIV vaccine, followed by infection with a hemagglutinin and neuraminidase mismatched challenge influenza virus. This elicits antibodies (Abs) that bind immunodominant epitopes in the HA2 region of the heterologous virus, which supposedly can cause enhanced virus fusion activity to the host cell and increased infection.

In this recently published research, CEEZAD scientists showed that αGC can induce severe VAERD in pigs. However, instead of stimulating high concentrations of HA2-specific Abs, αGC elicits high concentrations of interferon (IFN)-γ-secreting cells, both in the lungs and systemically. Additionally, the study  found that VAERD mediated by iNKT cells results in distinct cytokine profiles and altered adaptation of the challenge virus following infection when compared to an OIW adjuvant.

Overall, these results provide a cautionary note about considering the formulation of WIV vaccines with iNKT-cell agonists as a potential strategy to modulate antigen-specific immunity.

 

October 22, 2024

CEEZAD Director elected to National Academy of Medicine

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 (CEZID; https://www.k-state.edu/cezid/) has been elected to the National Academy of Medicine (NAM), the premier organization of scientists working in health-related fields. He is the first faculty member to be elected to the NAM while at K-State.

Dr. Juergen A. Richt, Regents and University Distinguished Professor at Kansas State University and director of CEEZAD and CEZID, was one of 100 new members elected by a vote of current members and announced by the NAM this week.

The citation accompanying Dr. Richt’s election singled him out as “a pioneer in infectious diseases of 'One Health' importance." It said, “his prolific basic and translational research findings on emerging pathogens of livestock, wildlife and humans are unique and highly significant for animal and public health, and his biocontainment expertise is crucial for the nation's bio- and agro-terrorism defense capacities.”

"We are incredibly proud of Dr. Richt for this remarkable accomplishment," said Hans Coetzee, interim vice president for research. "Being selected to join the National Academy of Medicine is a testament to his outstanding contributions to the field and his dedication to advancing medical science and improving healthcare. We are excited to see Juergen continue to innovate and inspire as a member of this prestigious institution."

As founding director of CEEZAD and CEZID, Dr. Richt supports the National Institutes of Health, the Department of Homeland Security and the U.S. Department of Agriculture in protecting public health and U.S. agricultural systems from devastating animal and zoonotic diseases.

He is editor-in-chief for Virus Genes and serves on editorial boards for other scientific journals, among them Advances in Virus Research, Emerging Microbes and Infections, and Animal Diseases. He has edited several books, obtained several patents, published more than 340 peer-reviewed manuscripts and raised more than $73 million in grants for veterinary research.

"This is a tremendous honor, and one which I will strive in my future work to live up to," Richt said. "I accept it as an outgrowth of a lifetime of commitment to the study of veterinary science and with full recognition of the part played by my numerous colleagues and collaborators in any success I may have achieved. This is a testament to my mentors – Drs. Rott and Narayan  -  and the many collaborators I was fortunate to have during my career, among them Drs. W. Garten (Marbug), H. Feldmann (NIH), K. Lager (USDA), A. Hamir (USDA), Bill Wilson (USDA), A. Garcia-Sastre (ISMMS),  R. Webby (St. Jude’s), W. Ma (KSU/U Missouri), and many others.”

Richt's work on high-consequence pathogens with zoonotic and transboundary potential has led to strategies to identify, control and eradicate such agents. His basic and applied research includes studies on animal influenza viruses — swine, bat and avian — and animal prion diseases, including bovine spongiform encephalopathy, Rift Valley Fever virus, African Swine fever virus, Mpox virus, SARS-CoV-2 and Borna Disease virus.

Richt established the first reverse genetics system for the swine influenza virus and made seminal contributions to the development of a modified live SIV vaccine. He has also contributed to the understanding of the virulence of the reconstructed 1918 Spanish flu virus in livestock.

Presently, Richt's lab is developing knock-out pigs that are less susceptible to SIV infections using CRISPR-Cas9 technology to protect both animal and human health. He also developed a mass-applicable Newcastle Disease virus-vectored vaccine for highly pathogenic avian influenza.

In the past few years, he has worked on the establishment of preclinical animal models for SARS-CoV-2 to determine the efficacy of COVID-19 vaccines and therapeutics as well as the susceptibility of livestock species to the Mpox virus.

In 2011, Richt received the Pfizer Animal Health Award for Research Excellence. In 2018, he was named a fellow of the American Association for the Advancement of Science. He received the 2021 Excellence in Research Award from the American Academy of Veterinary Medical Colleges, and that same year, he was named winner of the Dolph Simons Award for Biomedical Research by the University of Kansas. He is an extraordinary professor at the University of Pretoria and has received an A rating from the National Research Foundation of South Africa.

Richt received his Doctor of Veterinary Medicine degree from the University of Munich and a Ph.D. in virology and immunology from the University of Giessen, both in Germany. After coming to the United States in 1989, he completed three years of postdoctoral/residency studies at Johns Hopkins University and later served for eight years as a veterinary medical officer at the National Animal Disease Center in Ames, Iowa.

"We are thrilled Dr. Richt will be inducted into the National Academy of Medicine," said Bonnie Rush, Hodes family dean of the College of Veterinary Medicine. "Dr. Richt's talent and accomplishments are indisputable. He has continually demonstrated his ability to deliver relevant answers in response to emerging pathogens with national and global significance. However, his life's work is more than a tally of publications and research awards. His legacy lies in his commitment to training a generation of scientists with the expertise and inclination to pursue solutions for the most significant pathogens on the planet."

 

October 17, 2024

 

Findings of Dr. Richt’s research on spread of H5N1 virus are detailed in JAMA article

Recent research conducted by the Director of the Center of Excellence For Emerging and Zoonotic Animal Diseases (www.ceezad.org)  is the focus of an article published this week in JAMA Network, the online publication of the Journal of the American Medical Association.

The article detailed findings of research concerning the spread of the H5N1 virus by Dr. Juergen A. Richt, who in addition to his duties at CEEZAD is also the Regents and University Distinguished Professor at Kansas State University. That research established that the H5N1 clade 2.3.4.4b virus spreads in cattle primarily through the mammary glands of lactating cows.

Dr. Richt’s findings were reported on in detail in a recently published article in the journal, Nature

H5N1 is primarily a disease of birds, but it can also affect mammals, among them pigs, cows and occasionally humans.

 Since 2021 it has been also found in Canada and in the United States.

More than 1,100 flocks in 48 states have been affected by it, and about 100 million birds have been culled.

At the moment, there are more than 300 outbreaks in dairy cattle in the U.S. in 14 states, including four in Kansas.

You can read the full article by copying this link into your browser:

Huge amounts of bird-flu virus found in raw milk of infected cows (nature.com)

 

Thursday, September 26, 2024

H5N1 Influenza May Be Spreading Through Cows via Milking Rather Than Air, Experts Weigh In

The new findings trigger the ongoing debate about raw milk consumption and its potential risks.

 

 

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