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Reynoldsburg, OH, United States

Wang L.,Cincinnati Childrens Hospital Medical Center | Wang L.,Animal Disease Diagnostic Laboratory | Cao D.,Virginia Polytechnic Institute and State University | Wei C.,Cincinnati Childrens Hospital Medical Center | And 5 more authors.
Vaccine | Year: 2014

Norovirus (NoV) and hepatitis E virus (HEV) are both enterically-transmitted viruses causing gastroenteritis and hepatitis, respectively, in humans. While a vaccine against HEVs recently became available in China, there is no prophylactic or therapeutic approach against NoVs. Both NoV and HEV have surface protrusions formed by dimers of the protruding (P) domains of the viral capsids, which is responsible for virus-host interactions and eliciting viral neutralizing antibody. We developed in this study a bivalent vaccine against the two viruses through a recently developed polyvalent complex platform. The dimeric P domains of NoV and HEV were fused together, designated as NoV P--HEV P, which was then linked with the dimeric glutathione-S-transferase (GST). After expression and purification in E. coli, the GST-NoV P--HEV P fusion protein assembled into polyvalent complexes with a mean size of 1.8μm, while the NoV P--HEV P formed oligomers ranging from 100 to 420kDa. Mouse immunization study demonstrated that both GST-NoV P--HEV P and NoV P--HEV P complexes induced significantly higher antibody titers to NoV P- and HEV P, respectively, than those induced by a mixture of the NoV P- and HEV P dimers. Furthermore, the complex-induced antisera exhibited significantly higher neutralizing activity against HEV infection in HepG2/3A cells and higher blocking activity on NoV P particles binding to HBGA receptors than those of the dimer-induced antisera. Thus, GST-NoV P--HEV P and NoV P--HEV P complexes are promising dual vaccine candidates against both NoV and HEV. © 2013 Elsevier Ltd.

Xia M.,Cincinnati Childrens Hospital Medical Center | Wei C.,Cincinnati Childrens Hospital Medical Center | Wang L.,Cincinnati Childrens Hospital Medical Center | Wang L.,Animal Disease Diagnostic Laboratory | And 6 more authors.
Vaccine | Year: 2016

Hepatitis E virus (HEV), norovirus (NoV), and astrovirus (AstV) are enterically-transmitted viral pathogens causing epidemic or endemic hepatitis (HEV) and gastroenteritis (NoV and AstV) respectively in humans, leading to significant morbidity and mortality worldwide. While a recombinant subunit vaccine against HEVs is available in China, there is no commercial vaccine or antiviral against NoV or AstV. We report here our development of a trivalent vaccine against the three viral pathogens through our new polymer vaccine technology. All HEV, NoV, and AstV are non-enveloped RNA viruses covered by a protein capsid, featuring surface protruding (P) proteins that are responsible for virus-host interaction. These dimeric P proteins elicit neutralizing antibody and are good targets for subunit vaccine development. The trivalent subunit vaccine was developed by fusion of the dimeric P domains of the three viruses together that formed tetramers. This trivalent vaccine elicited significantly higher antibody responses in mice against all three P domains than those induced by a mixture of the three free P domains (mixed vaccine). Furthermore, the post-immune antisera of the trivalent vaccine showed significantly higher neutralizing titers against HEV infection in cell culture and higher blocking activity against NoV binding to HBGA ligands than those of the post-immune sera of the mixed vaccine. Thus, the trivalent vaccine is a promising vaccine candidate against HEV, NoV, and AstV. © 2016 Elsevier Ltd.

Li H.,Washington State University | Cunha C.W.,Washington State University | Abbitt B.,Texas College | Lenz S.D.,Purdue University | And 2 more authors.
Journal of Zoo and Wildlife Medicine | Year: 2013

In the recent investigation of malignant catarrhal fever in a red brocket deer (Mazama americana) from a Texas zoo, the viral DNA from the herpesvirus termed MCFV-WTD, which causes disease in white-tailed deer (Odocoileus virginianus), was detected. The epidemiology information revealed that the red brocket deer had been associated with a herd of pygmy goats (Capra hircus) at the zoo. MCFV-WTD DNA was also detected in one of these 12 goats that were malignant catarrhal fever viral antibody positive. The amplified herpesviral sequences from the affected deer and the MCFV-WTD-positive goat were identical, and matched the sequence in GenBank. Three of 123 DNA samples from various breeds of goats from different geographic locations in the United States were positive for MCFV-WTD DNA. The study shows that MCFV-WTD is capable of causing malignant catarrhal fever in other species of deer besides white-tailed deer and suggests that goats are a potential reservoir for the virus. © 2013 American Association of Zoo Veterinarians.

Killian M.L.,U.S. Department of Agriculture | Swenson S.L.,U.S. Department of Agriculture | Vincent A.L.,U.S. Department of Agriculture | Landgraf J.G.,U.S. Department of Agriculture | And 6 more authors.
Zoonoses and Public Health | Year: 2013

Influenza-like illness was noted in people and pigs in attendance at an Ohio county fair in August 2007. The morbidity rate in swine approached 100% within 1-2days of initial clinical signs being recognized, and approximately two dozen people developed influenza-like illness. Triple-reassortant swine H1N1 influenza viruses were identified in both pigs and people at the fair. The identified viruses (A/Sw/OH/511445/2007, A/Ohio/01/2007, and A/Ohio/02/2007) were similar to H1N1 swine influenza viruses currently found in the U.S. swine population. This case illustrates the possibility of transmission of swine influenza in settings where there is close human/swine interaction. © 2012 Blackwell Verlag GmbH.

Oka T.,Ohio State University | Oka T.,Japan National Institute of Infectious Diseases | Saif L.J.,Ohio State University | Marthaler D.,University of Minnesota | And 7 more authors.
Veterinary Microbiology | Year: 2014

The highly contagious and deadly porcine epidemic diarrhea virus (PEDV) first appeared in the US in April 2013. Since then the virus has spread rapidly nationwide and to Canada and Mexico causing high mortality among nursing piglets and significant economic losses. Currently there are no efficacious preventive measures or therapeutic tools to control PEDV in the US. The isolation of PEDV in cell culture is the first step toward the development of an attenuated vaccine, to study the biology of PEDV and to develop in vitro PEDV immunoassays, inactivation assays and screen for PEDV antivirals. In this study, nine of 88 US PEDV strains were isolated successfully on Vero cells with supplemental trypsin and subjected to genomic sequence analysis. They differed genetically mainly in the N-terminal S protein region as follows: (1) strains (n=7) similar to the highly virulent US PEDV strains; (2) one similar to the reportedly US S INDEL PEDV strain; and (3) one novel strain most closely related to highly virulent US PEDV strains, but with a large (197aa) deletion in the S protein. Representative strains of these three genetic groups were passaged serially and grew to titers of ~5-6log10 plaque forming units/mL. To our knowledge, this is the first report of the isolation in cell culture of an S INDEL PEDV strain and a PEDV strain with a large (197aa) deletion in the S protein. We also designed primer sets to detect these genetically diverse US PEDV strains. © 2014 Elsevier B.V.

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