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.
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, 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.
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|Ko, Eun-Ju; Kwon, Young-Man; Lee, Jong Seok et al. (2015) Virus-like nanoparticle and DNA vaccination confers protection against respiratory syncytial virus by modulating innate and adaptive immune cells. Nanomedicine 11:99-108|
|Kwon, Young-Man; Hwang, Hye Suk; Lee, Jong Seok et al. (2014) Maternal antibodies by passive immunization with formalin inactivated respiratory syncytial virus confer protection without vaccine-enhanced disease. Antiviral Res 104:1-6|
|Lee, Sujin; Quan, Fu-Shi; Kwon, Youngman et al. (2014) Additive protection induced by mixed virus-like particles presenting respiratory syncytial virus fusion or attachment glycoproteins. Antiviral Res 111:129-35|
|Meng, Jia; Lee, Sujin; Hotard, Anne L et al. (2014) Refining the balance of attenuation and immunogenicity of respiratory syncytial virus by targeted codon deoptimization of virulence genes. MBio 5:e01704-14|
|Meng, Jia; Stobart, Christopher C; Hotard, Anne L et al. (2014) An overview of respiratory syncytial virus. PLoS Pathog 10:e1004016|
|Wong, Terianne M; Boyapalle, Sandhya; Sampayo, Viviana et al. (2014) Respiratory syncytial virus (RSV) infection in elderly mice results in altered antiviral gene expression and enhanced pathology. PLoS One 9:e88764|
|Dulek, Daniel E; Newcomb, Dawn C; Toki, Shinji et al. (2014) STAT4 deficiency fails to induce lung Th2 or Th17 immunity following primary or secondary respiratory syncytial virus (RSV) challenge but enhances the lung RSV-specific CD8+ T cell immune response to secondary challenge. J Virol 88:9655-72|
|Zhou, Weisong; Goleniewska, Kasia; Zhang, Jian et al. (2014) Cyclooxygenase inhibition abrogates aeroallergen-induced immune tolerance by suppressing prostaglandin I2 receptor signaling. J Allergy Clin Immunol 134:698-705.e5|
|Yan, Dan; Lee, Sujin; Thakkar, Vidhi D et al. (2014) Cross-resistance mechanism of respiratory syncytial virus against structurally diverse entry inhibitors. Proc Natl Acad Sci U S A 111:E3441-9|
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