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2. Deletion of MGF505-2R Gene Activates the cGAS-STING Pathway Leading to Attenuation and Protection against Virulent African Swine Fever Virus

Author

Sunwoo, Sun-Young, primary, García-Belmonte, Raquel, additional, Walczak, Marek, additional, Vigara-Astillero, Gonzalo, additional, Kim, Dae-Min, additional, Szymankiewicz, Krzesimir, additional, Kochanowski, Maciej, additional, Liu, Lihong, additional, Tark, Dongseob, additional, Podgórska, Katarzyna, additional, Revilla, Yolanda, additional, and Pérez-Núñez, Daniel, additional

Published
2024
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3. Rift Valley Fever Phlebovirus Reassortment Study in Sheep.

Author

Balaraman, Velmurugan, Indran, Sabarish V., Kim, In Joong, Trujillo, Jessie D., Meekins, David A., Shivanna, Vinay, Zajac, Michelle D., Urbaniak, Kinga, Morozov, Igor, Sunwoo, Sun-Young, Faburay, Bonto, Osterrieder, Klaus, Gaudreault, Natasha N., Wilson, William C., and Richt, Juergen A.

Subjects
RIFT Valley fever, SHEEP, VETERINARY public health, SHEEP breeds, AEDES aegypti, PUBLIC health, INFECTIOUS disease transmission
Abstract

Rift Valley fever (RVF) in ungulates and humans is caused by a mosquito-borne RVF phlebovirus (RVFV). Live attenuated vaccines are used in livestock (sheep and cattle) to control RVF in endemic regions during outbreaks. The ability of two or more different RVFV strains to reassort when co-infecting a host cell is a significant veterinary and public health concern due to the potential emergence of newly reassorted viruses, since reassortment of RVFVs has been documented in nature and in experimental infection studies. Due to the very limited information regarding the frequency and dynamics of RVFV reassortment, we evaluated the efficiency of RVFV reassortment in sheep, a natural host for this zoonotic pathogen. Co-infection experiments were performed, first in vitro in sheep-derived cells, and subsequently in vivo in sheep. Two RVFV co-infection groups were evaluated: group I consisted of co-infection with two wild-type (WT) RVFV strains, Kenya 128B-15 (Ken06) and Saudi Arabia SA01-1322 (SA01), while group II consisted of co-infection with the live attenuated virus (LAV) vaccine strain MP-12 and a WT strain, Ken06. In the in vitro experiments, the virus supernatants were collected 24 h post-infection. In the in vivo experiments, clinical signs were monitored, and blood and tissues were collected at various time points up to nine days post-challenge for analyses. Cell culture supernatants and samples from sheep were processed, and plaque-isolated viruses were genotyped to determine reassortment frequency. Our results show that RVFV reassortment is more efficient in co-infected sheep-derived cells compared to co-infected sheep. In vitro, the reassortment frequencies reached 37.9% for the group I co-infected cells and 25.4% for the group II co-infected cells. In contrast, we detected just 1.7% reassortant viruses from group I sheep co-infected with the two WT strains, while no reassortants were detected from group II sheep co-infected with the WT and LAV strains. The results indicate that RVFV reassortment occurs at a lower frequency in vivo in sheep when compared to in vitro conditions in sheep-derived cells. Further studies are needed to better understand the implications of RVFV reassortment in relation to virulence and transmission dynamics in the host and the vector. The knowledge learned from these studies on reassortment is important for understanding the dynamics of RVFV evolution. [ABSTRACT FROM AUTHOR]

Published
2024
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7. Development of a chromatographic lateral flow immunoassay for detection of African swine fever virus antigen in blood

Author

National Bio and Agro-Defense Facility (US), National Institute of General Medical Sciences (US), Madden, Daniel W., Sunwoo, Sun Young [0000-0003-4688-641X], Gaudreault, Natasha N.[0000-0002-7195-785X], Trujillo, Jessie D.[0000-0002-4930-5839], Morozov, Igor [0000-0002-9343-5446], Gallardo, Carmina [0000-0003-3293-306X], Richt, Jürgen A. [0000-0001-7308-5672], Sunwoo, Sun Young, Gaudreault, Natasha N., Trujillo, Jessie D., Morozov, Igor, Gallardo, Carmina, Richt, Jürgen A., National Bio and Agro-Defense Facility (US), National Institute of General Medical Sciences (US), Madden, Daniel W., Sunwoo, Sun Young [0000-0003-4688-641X], Gaudreault, Natasha N.[0000-0002-7195-785X], Trujillo, Jessie D.[0000-0002-4930-5839], Morozov, Igor [0000-0002-9343-5446], Gallardo, Carmina [0000-0003-3293-306X], Richt, Jürgen A. [0000-0001-7308-5672], Sunwoo, Sun Young, Gaudreault, Natasha N., Trujillo, Jessie D., Morozov, Igor, Gallardo, Carmina, and Richt, Jürgen A.

Abstract

African swine fever (ASF) is a highly lethal disease of domestic and wild swine caused by African swine fever virus (ASFV). The disease currently circulates in Africa, Europe, Asia and on the island of Hispaniola. The ongoing epizootics in Europe and Asia have produced millions of animal deaths and severe economic losses. No effective vaccine is available for ASF, making rapid and accurate detection of ASFV essential for disease mitigation strategies. Currently available diagnostics for ASFV possess significant limitations related to assay performance, deployability, and/or turn-around time; therefore there is an unmet need for pen-side diagnostic tests with sufficient sensitivity and specificity. A chromatographic lateral flow immunoassay (LFIA) was developed for the detection of ASFV antigen in EDTA-treated whole blood using monoclonal antibodies targeting the viral p30 protein. The assay requires only water to perform and provides results in 25 min, making it well-suited for field use. The LFIA was capable of detecting genotype I and genotype II strains of ASFV in EDTA blood from experimentally infected pigs at varying time-points after infection, though it was unable to detect a genotype X ASFV strain. Diagnostic sensitivity correlated with clinical disease severity, body temperature, and viral DNA levels, and was over 90% in animals showing moderate to severe ASF-related symptoms after challenge with virulent genotype II virus. The LFIA also showed a robust diagnostic specificity of over 98%, which is essential to field testing for a high consequence to foregin animal disease. The LFIA targeting the viral p30 protein can reliably detect ASFV in whole blood from animals showing moderate to severe clinical signs of infection with virulent genotype I and II isolates, making it a promising candidate for use as a field-deployable antigen detection assay. Additional evaluation using field samples and different virus strains is required to further assess the utility o

Published
2022

10. Recombinant African Swine Fever Virus Arm/07/CBM/c2 Lacking CD2v and A238L Is Attenuated and Protects Pigs against Virulent Korean Paju Strain

Author

Pérez-Núñez, Daniel, primary, Sunwoo, Sun-Young, additional, García-Belmonte, Raquel, additional, Kim, Chansong, additional, Vigara-Astillero, Gonzalo, additional, Riera, Elena, additional, Kim, Dae-min, additional, Jeong, Jiyun, additional, Tark, Dongseob, additional, Ko, Young-Seung, additional, You, Young-Kook, additional, and Revilla, Yolanda, additional

Published
2022
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11. Susceptibility of White-Tailed Deer to Rift Valley Fever Virus

Author

Wilson, William C., Kim, In Joong, Trujillo, Jessie D., Sunwoo, Sun Young, Noronha, Leela E., Urbaniak, Kinga, McVey, D. Scott, Drolet, Barbara S., Morozov, Igor, Faburay, Bonto, Schirtzinger, Erin E., Koopman, Tammy, Indran, Sabarish V., Balaraman, Velmurugan, and Richt, Juergen A.

Subjects
White-tailed deer -- Research -- Health aspects, Rift valley fever -- Risk factors -- Distribution, Disease susceptibility -- Analysis, Company distribution practices, Health
Abstract

Rift Valley fever virus (RVFV) is a zoonotic, arthropodborne RNA virus (order Bunyavirales, family Phenuiviridae, genus Phlebovirus) (1,2). The virus is maintained in nature in a mosquito-vertebrate host cycle and [...]

Published
2018
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15. Preliminary Evaluation of a Recombinant Rift Valley Fever Virus Glycoprotein Subunit Vaccine Providing Full Protection against Heterologous Virulent Challenge in Cattle

Author

Wilson, William C., primary, Faburay, Bonto, additional, Trujillo, Jessie D., additional, Ragan, Izabela, additional, Sunwoo, Sun-Young, additional, Morozov, Igor, additional, Shivanna, Vinay, additional, Balogh, Aaron, additional, Urbaniak, Kinga, additional, McVey, D. Scott, additional, Bold, Dashzeveg, additional, Gaudreault, Natasha N., additional, Schirtzinger, Erin E., additional, Ma, Wenjun, additional, and Richt, Juergen A., additional

Published
2021
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16. High dose of vesicular stomatitis virus-vectored Ebola virus vaccine causes vesicular disease in swine without horizontal transmission

Author

Morozov, Igor, primary, Monath, Thomas P., additional, Meekins, David A., additional, Trujillo, Jessie D., additional, Sunwoo, Sun-Young, additional, Urbaniak, Kinga, additional, Kim, In Joong, additional, Narayanan, Sanjeev K., additional, Indran, Sabarish V., additional, Ma, Wenjun, additional, Wilson, William C., additional, O'Connor, Cassandra, additional, Dubey, Sheri, additional, Troth, Sean P., additional, Coller, Beth-Ann, additional, Nichols, Richard, additional, Martin, Brian K., additional, Feldmann, Heinz, additional, and Richt, Juergen A., additional

Published
2021
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17. Evaluation of A Baculovirus-Expressed VP2 Subunit Vaccine for the Protection of White-Tailed Deer (Odocoileus virginianus) from Epizootic Hemorrhagic Disease

Author

Sunwoo, Sun Young, primary, Noronha, Leela E., additional, Morozov, Igor, additional, Trujillo, Jessie D., additional, Kim, In Joong, additional, Schirtzinger, Erin E., additional, Faburay, Bonto, additional, Drolet, Barbara S., additional, Urbaniak, Kinga, additional, McVey, D. Scott, additional, Meekins, David A., additional, Palmer, Mitchell V., additional, Balaraman, Velmurugan, additional, Wilson, William C., additional, and Richt, Juergen A., additional

Published
2020
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18. DNA-Protein Vaccination Strategy Does Not Protect from Challenge with African Swine Fever Virus Armenia 2007 Strain

Author

Consejo Superior de Investigaciones Científicas (España), US Department of Homeland Security, Center of Excellence for Emerging and Zoonotic Animal Diseases (US), National Bio and Agro-Defense Facility (US), Sunwoo, Sun-Young, Pérez-Núñez, Daniel, Morozov, Igor, Sánchez, Elena G., Gaudreault, Natasha N., Trujillo, Jessie D., Mur, Lina, Nogal, Marisa, Madden, Daniel, Urbaniak, Kinga, Kim, In Joong, Ma, Wenjun, Revilla Novella, Yolanda, Richt, Juergen A., Consejo Superior de Investigaciones Científicas (España), US Department of Homeland Security, Center of Excellence for Emerging and Zoonotic Animal Diseases (US), National Bio and Agro-Defense Facility (US), Sunwoo, Sun-Young, Pérez-Núñez, Daniel, Morozov, Igor, Sánchez, Elena G., Gaudreault, Natasha N., Trujillo, Jessie D., Mur, Lina, Nogal, Marisa, Madden, Daniel, Urbaniak, Kinga, Kim, In Joong, Ma, Wenjun, Revilla Novella, Yolanda, and Richt, Juergen A.

Abstract

African swine fever virus (ASFV) causes high morbidity and mortality in swine (Sus scrofa), for which there is no commercially available vaccine. Recent outbreaks of the virus in Trans-Caucasus countries, Eastern Europe, Belgium and China highlight the urgent need to develop effective vaccines against ASFV. Previously, we evaluated the immunogenicity of a vaccination strategy designed to test various combinations of ASFV antigens encoded by DNA plasmids and recombinant proteins with the aim to activate both humoral and cellular immunity. Based on our previous results, the objective of this study was to test the combined DNA-protein vaccine strategy using a cocktail of the most immunogenic antigens against virulent ASFV challenge. Pigs were vaccinated three times with a cocktail that included ASFV plasmid DNA (CD2v, p72, p32, +/−p17) and recombinant proteins (p15, p35, p54, +/−p17). Three weeks after the third immunization, all pigs were challenged with the virulent ASFV Armenia 2007 strain. The results showed that vaccinated pigs were not protected from ASFV infection or disease. Compared to the non-vaccinated controls, earlier onset of clinical signs, viremia, and death were observed for the vaccinated animals following virulent ASFV challenge. ASFV induced pathology was also enhanced in the vaccinated pigs. Furthermore, while the vaccinated pigs developed antigen-specific antibodies, immunized pig sera at the time of challenge lacked the capacity to neutralize virus, and instead was observed to enhance ASFV infection in vitro. The results of this work points to a putative immune enhancement mechanism involved in ASFV pathogenesis that warrants further investigation. This pilot study provides insight for the selection of appropriate combinations of ASFV antigens for the development of a rationally-designed, safe, and efficacious vaccine for ASF.

Published
2019

20. DNA-Protein Vaccination Strategy Does Not Protect from Challenge with African Swine Fever Virus Armenia 2007 Strain

Author

Sunwoo, Sun-Young, primary, Pérez-Núñez, Daniel, additional, Morozov, Igor, additional, Sánchez, Elena, additional, Gaudreault, Natasha, additional, Trujillo, Jessie, additional, Mur, Lina, additional, Nogal, Marisa, additional, Madden, Daniel, additional, Urbaniak, Kinga, additional, Kim, In, additional, Ma, Wenjun, additional, Revilla, Yolanda, additional, and Richt, Juergen, additional

Published
2019
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21. Immunogenicity and efficacy of Schmallenberg virus envelope glycoprotein subunit vaccines

Author

Endalew, Abaineh D., primary, Faburay, Bonto, additional, Trujillo, Jessie D., additional, Gaudreault, Natasha N., additional, Davis, A. Sally, additional, Shivanna, Vinay, additional, Sunwoo, Sun-Young, additional, Ma, Wenjun, additional, Drolet, Barbara S., additional, McVey, D. Scott, additional, Morozov, Igor, additional, Wilson, William C., additional, and Richt, Juergen A., additional

Published
2019
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23. Erratum: Sunwoo, S.-Y. et al. A Universal Influenza Virus Vaccine Candidate Tested in a Pig Vaccination-Infection Model in the Presence of Maternal Antibodies. Vaccines 2018, 6(3), 64

Author

Sunwoo, Sun-Young, primary, Schotsaert, Michael, additional, Morozov, Igor, additional, Davis, Anne, additional, Li, Yuhao, additional, Lee, Jinhwa, additional, McDowell, Chester, additional, Meade, Philip, additional, Nachbagauer, Raffael, additional, García-Sastre, Adolfo, additional, Ma, Wenjun, additional, Krammer, Florian, additional, and Richt, Juergen, additional

Published
2018
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25. A Universal Influenza Virus Vaccine Candidate Tested in a Pig Vaccination-Infection Model in the Presence of Maternal Antibodies

Author

Sunwoo, Sun-Young, primary, Schotsaert, Michael, additional, Morozov, Igor, additional, Davis, Anne, additional, Li, Yuhao, additional, Lee, Jinhwa, additional, McDowell, Chester, additional, Meade, Philip, additional, Nachbagauer, Raffael, additional, García-Sastre, Adolfo, additional, Ma, Wenjun, additional, Krammer, Florian, additional, and Richt, Juergen, additional

Published
2018
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26. A Recombinant Rift Valley Fever Virus Glycoprotein Subunit Vaccine Confers Full Protection against Rift Valley Fever Challenge in Sheep

Author

Faburay, Bonto, primary, Wilson, William C., additional, Gaudreault, Natasha N., additional, Davis, A. Sally, additional, Shivanna, Vinay, additional, Bawa, Bhupinder, additional, Sunwoo, Sun Young, additional, Ma, Wenjun, additional, Drolet, Barbara S., additional, Morozov, Igor, additional, McVey, D. Scott, additional, and Richt, Juergen A., additional

Published
2016
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27. Development of a sheep challenge model for Rift Valley fever

Author

Faburay, Bonto, primary, Gaudreault, Natasha N., additional, Liu, Qinfang, additional, Davis, A. Sally, additional, Shivanna, Vinay, additional, Sunwoo, Sun Young, additional, Lang, Yuekun, additional, Morozov, Igor, additional, Ruder, Mark, additional, Drolet, Barbara, additional, Scott McVey, D., additional, Ma, Wenjun, additional, Wilson, William, additional, and Richt, Juergen A., additional

Published
2016
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32. Development of a chromatographic lateral flow immunoassay for detection of African swine fever virus antigen in blood

Author

Daniel W. Madden, Sun-Young Sunwoo, Natasha N. Gaudreault, Jessie D. Trujillo, Igor Morozov, Carmina Gallardo, Juergen A. Richt, National Bio and Agro-Defense Facility (US), National Institute of General Medical Sciences (US), Madden, Daniel W., Sunwoo, Sun Young, Gaudreault, Natasha N., Trujillo, Jessie D., Morozov, Igor, Gallardo, Carmina, and Richt, Juergen A.

Subjects
Lateral flow immunoassay, African swine fever, Point of care diagnostics
Abstract

15 Pág. Centro de Investigación en Sanidad Animal (CISA), African swine fever (ASF) is a highly lethal disease of domestic and wild swine caused by African swine fever virus (ASFV). The disease currently circulates in Africa, Europe, Asia and on the island of Hispaniola. The ongoing epizootics in Europe and Asia have produced millions of animal deaths and severe economic losses. No effective vaccine is available for ASF, making rapid and accurate detection of ASFV essential for disease mitigation strategies. Currently available diagnostics for ASFV possess significant limitations related to assay performance, deployability, and/or turn-around time; therefore there is an unmet need for pen-side diagnostic tests with sufficient sensitivity and specificity. A chromatographic lateral flow immunoassay (LFIA) was developed for the detection of ASFV antigen in EDTA-treated whole blood using monoclonal antibodies targeting the viral p30 protein. The assay requires only water to perform and provides results in 25 min, making it well-suited for field use. The LFIA was capable of detecting genotype I and genotype II strains of ASFV in EDTA blood from experimentally infected pigs at varying time-points after infection, though it was unable to detect a genotype X ASFV strain. Diagnostic sensitivity correlated with clinical disease severity, body temperature, and viral DNA levels, and was over 90% in animals showing moderate to severe ASF-related symptoms after challenge with virulent genotype II virus. The LFIA also showed a robust diagnostic specificity of over 98%, which is essential to field testing for a high consequence to foregin animal disease. The LFIA targeting the viral p30 protein can reliably detect ASFV in whole blood from animals showing moderate to severe clinical signs of infection with virulent genotype I and II isolates, making it a promising candidate for use as a field-deployable antigen detection assay. Additional evaluation using field samples and different virus strains is required to further assess the utility of this rapid diagnostic test., Funding for this study was provided through grants from the National Bio and Agro-Defense Facility (NBAF) Transition Fund from the State of Kansas, and the AMP Core of the Center of Emerging and Zoonotic Infectious Diseases (CEZID) from National Institute of General Medical Sciences (NIGMS) under award number P20GM130448.

Published
2022

34. Experimental Infection of Calves by Two Genetically-Distinct Strains of Rift Valley Fever Virus.

Author

Wilson WC, Davis AS, Gaudreault NN, Faburay B, Trujillo JD, Shivanna V, Sunwoo SY, Balogh A, Endalew A, Ma W, Drolet BS, Ruder MG, Morozov I, McVey DS, and Richt JA

Subjects
Animal Experimentation, Animals, Animals, Newborn, Cattle, Enzymes blood, Liver pathology, Rift Valley fever virus growth & development, Time Factors, Viral Load, Viremia pathology, Viremia virology, Cattle Diseases pathology, Cattle Diseases virology, Genotype, Rift Valley Fever pathology, Rift Valley Fever virology, Rift Valley fever virus genetics, Rift Valley fever virus pathogenicity
Abstract

Recent outbreaks of Rift Valley fever in ruminant livestock, characterized by mass abortion and high mortality rates in neonates, have raised international interest in improving vaccine control strategies. Previously, we developed a reliable challenge model for sheep that improves the evaluation of existing and novel vaccines in sheep. This sheep model demonstrated differences in the pathogenesis of Rift Valley fever virus (RVFV) infection between two genetically-distinct wild-type strains of the virus, Saudi Arabia 2001 (SA01) and Kenya 2006 (Ken06). Here, we evaluated the pathogenicity of these two RVFV strains in mixed breed beef calves. There was a transient increase in rectal temperatures with both virus strains, but this clinical sign was less consistent than previously reported with sheep. Three of the five Ken06-infected animals had an early-onset viremia, one day post-infection (dpi), with viremia lasting at least three days. The same number of SA01-infected animals developed viremia at 2 dpi, but it only persisted through 3 dpi in one animal. The average virus titer for the SA01-infected calves was 1.6 logs less than for the Ken06-infected calves. Calves, inoculated with either strain, seroconverted by 5 dpi and showed time-dependent increases in their virus-neutralizing antibody titers. Consistent with the results obtained in the previous sheep study, elevated liver enzyme levels, more severe liver pathology and higher virus titers occurred with the Ken06 strain as compared to the SA01 strain. These results demonstrate the establishment of a virulent challenge model for vaccine evaluation in calves.

Published
2016
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