A reduction in disease severity is the most likely indicator that an RSV vaccine is effective in young infants, the highest priority target population. However, we don't have precise markers to objectively assess RSV disease severity, which has made the evaluation of RSV vaccines in infants challenging. By applying a systems immunology approach our goal is to define the immune profiles, serum antibody responses, and RSV NS variants in infants with mild RSV infection, who represent the ideal model of a desirable vaccine induced outcomes. Based on our preliminary data we hypothesize that robust interferon (IFN) and innate immune responses, related in part to viral NS1 and/or NS2 variants, result in optimal B-cell activation, antibody responses (measured in Core C), and improved clinical outcomes in RSV infected infants. Identification of the ?safe and protective? profile to natural RSV infection will inform the selection of vaccine candidates (develop in Projects 1,2,3) in cotton rats (Core B) that should induce similar (or improved) profiles. In addition, these prototype profiles will serve as surrogate markers for the ?safe and protective? response in future vaccine trials testing the live attenuated RSV vaccine developed in this P01. We will test our hypothesis with the following specific aims: 1) Define the blood transcriptional signatures that correlate with mild RSV infection; 2) Define quantity and neutralizing activity of specific RSV antibodies associated with acute and long-term protection from severe RSV infection; 3) Identify the RSV NS1 and NS2 gene haplotypes that best correlate with disease severity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI112524-04
Application #
9541799
Study Section
Special Emphasis Panel (ZAI1)
Program Officer
Kim, Sonnie
Project Start
Project End
Budget Start
2018-02-01
Budget End
2019-01-31
Support Year
4
Fiscal Year
2018
Total Cost
Indirect Cost
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