The CIDER CEIRR consists of three human study projects and one multidisciplinary research project, as well as pre-pandemic and pandemic preparedness and risk assessment capabilities. Each site also yields unique human samples relevant to the questions asked at the study site, as well as to support the research projects and other collaborative endeavors.
The Pediatric Intensive Care Influenza (USIP) Cohort
This cohort, led by Adrienne Randolph (Boston Children’s Hospital), is an established network to sample young patients with severe disease caused by influenza virus infection to enable interrogation of the virus-host interactions and responses that lead to severe disease. The cohort will enroll new patients each influenza season, collecting acute and subsequent samples from ICU patients, including endotracheal tube aspirates. The USIP cohort includes young patients (≤21 years old) with influenza critical illness from 10 of 11 prior influenza seasons, as well as samples from ICU patients with non-influenza disease and control (biobank) samples. These and the prospective samples will be shared with CIDER research projects and collaboratively across the CEIRR network. While focused on influenza, the USIP cohort will test samples for other respiratory viruses, enabling tracking and assessment of other epidemic or pandemic viruses, including SARS-CoV-2. Importantly, the USIP network can also serve as a component of the pandemic response plan, as Dr. Randolph has an established pandemic response protocol (USIP-PREP) for sample and data collection.
Influenza disease in Aboriginal (high risk) and severe infections in Australia (DISI & LIFT)
These cohorts are led by Katherine Kedzierska at the University of Melbourne and consist of two established and complementary cohorts:
- Dissection of Influenza-Specific Immunity (DISI) cohort, which is a part of the Australian FLUCAN and collects clinical and epidemiological data on patients hospitalized with influenza nationally
- The Looking into InFluenza T cell immunity (LIFT) cohort representing adult Indigenous Australians (a high-risk population), including healthy donors (LIFT) and individuals receiving seasonal influenza vaccine (LIFT-V).
The goals of these studies are to understand mechanisms underlying disease severity and poor vaccine efficacy in the Southern Hemisphere to inform rational development of early biomarkers for influenza disease severity and improved interventions for at-risk patients. The DISI samples will be available for CIDER research projects and collaboratively across CEIRR. The LIFT samples must remain in Australia, but collaborative research with Dr. Kedzierska enables access to samples and collaborative research. While focused on influenza, the DISI and LIFT cohorts will test samples for other respiratory viruses, enabling tracking and assessment of other epidemic or pandemic viruses, including SARS-CoV-2.
Immune Responses in Indigenous Vaccine-naĂŻve Populations
This cohort, led by Stacey Schultz-Cherry (St. Jude Children’s Research Hospital), is an established network of indigenous tribes in Sierra Nevada de Santa Marta on Colombia’s Caribbean coast. These isolated populations are historically unvaccinated and have atypical serological responses to influenza viruses compared to the general Colombian population (e.g., absence of influenza B titers). The goal of this cohort is to assess vaccination in a vaccine-naïve population. Samples will be collected longitudinally before and after vaccination and shared with CIDER projects as well as collaboratively with the CEIRR network. While focused on influenza, the Colombian cohort will test samples for other respiratory viruses, enabling tracking and assessment of other epidemic or pandemic viruses, including SARS-CoV-2.
Exposing Influenza B: Interrogating the Evolution and Changing Host Response to the Other Influenza Virus
This multidisciplinary project led by Mark Tompkins (PI; UGA) is a collaboration with Pej Rohani (UGA), Andrea Sant (U Rochester), and Paul Thomas (SJCRH). While influenza A virus (IAV) has been extensively studied, influenza B virus (IBV) remains poorly understood, and yet in recent years, we have observed striking evolution of the Victoria and Yamagata lineages and atypical IBV seasons. Moreover, preliminary murine data suggests the cellular immune responses to IBV are distinct from those seen in IAV infection. Finally, tantalizing data suggest a possible role for interference in the epidemiology of IAV and IBV. This project utilizes a multidisciplinary approach, combining mouse and ferret infection and pathogenesis studies, and epidemiological and computational approaches to understand the differences between IAV and IBV infection and how the evolution of the IBV lineages and changing epidemiology is influencing infection, transmission and disease in humans. The project will utilize existing data as well as new data and potentially samples collected through CIDER. Importantly, this project presents several opportunities for within-CIDER and cross-CEIRR collaborative projects that will be developed through the CEIRR network. While this project focuses on the interactions of influenza virus types and lineages, the overall approach to understanding population-level consequences of within-host virus-virus interactions is readily transportable to other respiratory viral systems.
Awarded Options Projects
- A platform to study single-cell responses to infection or vaccination in the nose
PI(s): Dr. Jose Ordovas-Montanes, Boston Children's Hospital - Influenza and Respiratory Infections during Pregnancy: Impact on the Mother and Offspring
PI(s): Dr. Stacey Schultz-Cherry, St. Jude Children's Hospital - Early innate responses to IAV and IBV
PI(s): Dr. Andrea Sant, University of Rochester - Measurement of virus-specific T cells in the upper respiratory tractÂ
PI(s): Dr. Paul Thomas, St. Jude Children's Hospital - Understanding Influenza Virus Evolution Pathogenicity in the Presence of Preexisting Immunity
PI(s): Constantinos S. Kyriakis DVM, PhD and Co-PI(s): Dr. Laura Huber DVM, MSc, PhD, DACVPM and Dr. Miria Criado, MSc, PhD Auburn University - Characterization of Potentially Zoonotic Influenza A Viruses in Avian SpeciesÂ
PI(s): Dr. David Suarez and Dr. Erica Spackman, Southeast Poultry Research Lab, USDA-ARS - Immune Signals, Fibroblasts, and Endothelial Cells in the Outcome of Severe Influenza Infection
PI(s): Dr. Paul Thomas and Dr. Stacey Schultz-Cherry, St. Jude Children's Research Hospital - The early innate response to IAV and IBV infection
PI(s): Dr. Andrea Sant, University of Rochester - Computational Methods for Influenza Forecasting
PI(s): Dr. Pejman Rohani and Dr. John Drake, University of Georgia - Avian Influenza, is the population immunologically prepared for potential pandemics?Â
PI(s): Dr. Aitor Nogales, Consejo Superior de Investigaciones CientĂficas - Is IBV a human-only virus, or does it infect other species without adaptation?Â
PI(s): Dr. Mark Tompkins, University of Georgia - Â Investigation of repeated influenza vaccination for epitope focusingÂ
PI(s): Dr. Sophie Valkenburg, University of Melbourne - Â Incorporating virus receptor specificity into avian influenza virus phylodynamics
PI(s): Dr. Justin Bahl and Dr. Geert-Jan Boons, University of Georgia - Defining immune correlates of influenza B disease severity in children and adults
- PI(s): Dr Katherine Kedzierska, University of Melbourne and Dr Aubrey Gordon and University of Michigan