The overall goal of this P01 is to develop an attenuated vaccine capable of protecting infants and children from respiratory syncytial virus disease, including the tools necessary to test this vaccine effectively in cotton rats and eventually in infants and children. Core B (Animal Model Use and Development Core) supports the development and use of the cotton rat model utilized within this Program Project Grant (P01). The guiding principals for the animal model core are efficient planning and utilization of animals, standardization of processing, reliability of service and consistent evaluation of in vivo data thus serving as a platform to integrate data across the P01. The fundamental expertise provided within the core is laboratory animal medicine and clinical and anatomic pathology. The Core is housed and coordinated in the Department of Veterinary Biosciences. Dr. Stefan Niewiesk, proposed Core Director has been working with viral respiratory infections in cotton rats for the last 15 years and is an active collaborator with the principal investigators for the P01. He is certified in Veterinary Microbiology (German boards) and a diplomate of the European College of Laboratory Animal Medicine. Dr. Krista La Perle (co-investigator), who is a diplomate of the American College of Veterinary Pathology and has worked with Dr. Niewiesk on cotton rat pathology, will provide pathological evaluations for the Core. In Projects 1-3 (Drs. Teng, Peeples, Li), a genetically engineered RSV with reduced pathogenicity and increased immunogenicity will be generated by introducing mutations in the NS-1 protein, G protein, and the polymerase. In Project 4 (Dr. Mejias), the gene expression signature and antibody response of children with mild and severe disease will be determined and compared to the response of cotton rats to vaccination. Core B has developed assays and reagents necessary to support the various projects, and translate markers of immunity defined in patients back to the cotton rat model to improve the evaluation of vaccine candidates.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI112524-02
Application #
9133260
Study Section
Special Emphasis Panel (ZAI1-MFH-M)
Project Start
Project End
Budget Start
2016-02-01
Budget End
2017-01-31
Support Year
2
Fiscal Year
2016
Total Cost
$251,207
Indirect Cost
$42,357
Name
Nationwide Children's Hospital
Department
Type
DUNS #
147212963
City
Columbus
State
OH
Country
United States
Zip Code
43205
Hussain, Syed-Rehan A; Mejias, Asuncion; Ramilo, Octavio et al. (2018) Post-viral atopic airway disease: pathogenesis and potential avenues for intervention. Expert Rev Clin Immunol :1-10
Garcia-Mauriño, Cristina; Moore-Clingenpeel, Melissa; Wallihan, Rebecca et al. (2018) Discharge Criteria for Bronchiolitis: An Unmet Need. Pediatr Infect Dis J 37:514-519
Wang, Yilong; Liu, Rongxian; Lu, Mijia et al. (2018) Enhancement of safety and immunogenicity of the Chinese Hu191 measles virus vaccine by alteration of the S-adenosylmethionine (SAM) binding site in the large polymerase protein. Virology 518:210-220
Li, Anzhong; Yu, Jingyou; Lu, Mijia et al. (2018) A Zika virus vaccine expressing premembrane-envelope-NS1 polyprotein. Nat Commun 9:3067
Korppi, Matti (2018) Discharge Criteria for Bronchiolitis: Does Age Matter? Pediatr Infect Dis J 37:e350
Garcia-Mauriño, Cristina; Moore-Clingenpeel, Melissa; Ramilo, Octavio et al. (2018) Re: ""Discharge Criteria for Bronchiolitis: Does Age Matter?"" Pediatr Infect Dis J 37:e350-e351
Grieves, Jessica L; Yin, Zhiwei; Garcia-Sastre, Adolfo et al. (2018) A viral-vectored RSV vaccine induces long-lived humoral immunity in cotton rats. Vaccine 36:3842-3852
Garcia-Mauriño, Cristina; Moore-Clingenpeel, Melissa; Thomas, Jessica et al. (2018) Viral Load Dynamics and Clinical Disease Severity in Infants with Respiratory Syncytial Virus Infection. J Infect Dis :
Mazur, Natalie I; Higgins, Deborah; Nunes, Marta C et al. (2018) The respiratory syncytial virus vaccine landscape: lessons from the graveyard and promising candidates. Lancet Infect Dis 18:e295-e311
Hicks, Stephanie N; Chaiwatpongsakorn, Supranee; Costello, Heather M et al. (2018) Five Residues in the Apical Loop of the Respiratory Syncytial Virus Fusion Protein F2 Subunit Are Critical for Its Fusion Activity. J Virol 92:

Showing the most recent 10 out of 21 publications