CORE B: The purpose of this core is to establish and administer a prospective cohort, clinical database, and biospecimen repository that will enable research on the role of RSV in atopic and chronic lung disease inception. The core will support scientific projects that focus on host factors (Project 1), viral factors (Project 2), and mechanisms through which target interventions may work (Project 3). This core will prospectively enroll and follow 2000 term otherwise healthy infants who will be <6 months of age during winter virus season through age 3-4 years, at which time recurrent childhood wheeze and allergic sensitization will be defined - named the ReSPIRA cohort (Respiratory Study for Protection of Infants from RSV to Asthma). The core will provide detailed clinical information and biospecimens on a tightly phenotyped group of infants with a high likelihood of developing asthma, and thus allows the projects which this core serves to identify host genetic, viral genetic, cellular, immune, and molecular determinants of recurrent wheezing, early childhood asthma and atopy following infant RSV infection. The first two years of the clinical core will focus on enrollment, and the 3 subsequent years will focus on cohort follow-up and delivery of data and biospecimens to co-investigators, whose projects will address research questions related to RSV illness and early childhood asthma.
Our specific aims are to: (1) Create the ReSPIRA cohort;(2) Clinically characterize (phenotype) the infant cohort in Argentina with regards to RSV infection status, host response, and lung injury during infancy, on the outcomes of recurrent childhood wheezing, asthma, and atopy;and (3) Establish and maintain a biospecimen repository and distribute its'resources to conduct studies on the mechanisms through which RSV infection may lead to recurrent wheezing and asthma development. This core supports the overall Center by centralizing resources on cohort inception, detailed classification of RSV infection/exposure, outcomes assessments, data management and administration, to support the study of the role of infant RSV illness on later childhood atopy and asthma outcomes. As bronchiolitis and asthma are the most common, serious, acute and chronic conditions of infancy and childhood, respectively, and are diseases that disproportionately burden vulnerable populations, this core and supported projects will have major, long-lasting impact by improving our understanding of the role of, and the mechanisms through which RSV contributes to later childhood outcomes.

Public Health Relevance

The purpose of this core is to centralize resources to establish and administer a cohort of infants followed into childhood, and a clinical database and specimen repository that will enable research on the role of a ubiquitous respiratory viral infection. Respiratory Syncytial Virus (RSV), on the development of asthma and allergic diseases. The resources will support the proposed scientific projects in the Center focused on the question of how RSV causes asthma, and be a shared resource available to other NIH-supported investigations.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI095227-04
Application #
8705261
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Type
DUNS #
City
Nashville
State
TN
Country
United States
Zip Code
37212
Shilts, Meghan H; Rosas-Salazar, Christian; Tovchigrechko, Andrey et al. (2016) Minimally Invasive Sampling Method Identifies Differences in Taxonomic Richness of Nasal Microbiomes in Young Infants Associated with Mode of Delivery. Microb Ecol 71:233-42
Mathias, Rasika Ann; Taub, Margaret A; Gignoux, Christopher R et al. (2016) A continuum of admixture in the Western Hemisphere revealed by the African Diaspora genome. Nat Commun 7:12522
Rosas-Salazar, Christian; Shilts, Meghan H; Tovchigrechko, Andrey et al. (2016) Nasopharyngeal Microbiome in Respiratory Syncytial Virus Resembles Profile Associated with Increased Childhood Asthma Risk. Am J Respir Crit Care Med 193:1180-3
Rostad, Christina A; Stobart, Christopher C; Gilbert, Brian E et al. (2016) A Recombinant Respiratory Syncytial Virus Vaccine Candidate Attenuated by a Low-Fusion F Protein Is Immunogenic and Protective against Challenge in Cotton Rats. J Virol 90:7508-18
Lee, Sujin; Nguyen, Minh Trang; Currier, Michael G et al. (2016) A polyvalent inactivated rhinovirus vaccine is broadly immunogenic in rhesus macaques. Nat Commun 7:12838
Stobart, Christopher C; Rostad, Christina A; Ke, Zunlong et al. (2016) A live RSV vaccine with engineered thermostability is immunogenic in cotton rats despite high attenuation. Nat Commun 7:13916
Tan, Yi; Hassan, Ferdaus; Schuster, Jennifer E et al. (2016) Molecular Evolution and Intraclade Recombination of Enterovirus D68 during the 2014 Outbreak in the United States. J Virol 90:1997-2007
Banathy, Alex; Cheung-Flynn, Joyce; Goleniewska, Kasia et al. (2016) Heat Shock-Related Protein 20 Peptide Decreases Human Airway Constriction Downstream of β2-Adrenergic Receptor. Am J Respir Cell Mol Biol 55:225-33
Zhou, Weisong; Zhang, Jian; Goleniewska, Kasia et al. (2016) Prostaglandin I2 Suppresses Proinflammatory Chemokine Expression, CD4 T Cell Activation, and STAT6-Independent Allergic Lung Inflammation. J Immunol 197:1577-86
Stier, Matthew T; Bloodworth, Melissa H; Toki, Shinji et al. (2016) Respiratory syncytial virus infection activates IL-13-producing group 2 innate lymphoid cells through thymic stromal lymphopoietin. J Allergy Clin Immunol 138:814-824.e11

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