025806864609S
Option 20E â SIG/SAVE effort Subaward No. 0258-0686-4609 For this project, we will evaluate antibody responses against up to 20 SARS-CoV-2 variant strains. We will utilize neutralization assays, either CPE based assays or plaque reducing neutralizing titer (PRNT50) assays, to determine the protective capacity of serum provided by the SAVES program against live SARS-CoV-2 variant viruses with the goal of identifying variants that may be capable of escaping vaccine mediated immunity. All research procedures will be aligned with the SAVES program in vitro group. Option 20E â SAVE Program Subaward No. 0258-0689-4609 For this project, we will evaluate the efficacy of vaccines against SARS-CoV-2 variants of interest in both vaccinate and infect and vaccinate and hold models in an effort to identify variants that may escape vaccine mediated immunity. We will immunize mice using the Novavax Nanoparticle S vaccine and perform serial bleeds to confirm serum antibody levels against SARS-CoV2 using neutralization assays. Mice will be infected with WA-1 or a selected variant of concern strain SARS-CoV-2 at high and low doses. Mice will be weighed daily and organs harvested for further analysis of viral titer. All research procedures will be aligned with the SAVES program in vivo group.
University Of Maryland, Baltimore
Definitive Contract HHSN272201400008C
$508.0k 9/29/21 025806624609S
Non-Severable Option 18K Pilot Project: 0258-0662-4609 1.Identify within-person viral variants in nasopharyngeal swabs (NPS), oropharyngeal swabs (OPS) and coarse and fine particle aerosols using influenza-specific deep sequencing to a) test the hypothesis that influenza virus variants found in NPS, OPS, and coarse and fine particle exhaled breath aerosols represent independent sets of variants, and b) identify and characterize non-synonymous variants, and variant stability over the course of up to three days post onset of symptoms, and c) characterize the frequency of SNPs differentiating consensus sequences in the upper and lower respiratory tract and the potential of sequence analysis for identifying not only chains of transmission but also whether transmission was from the upper or lower airways of the index case; 2.Characterize host mucosal immunity in throat swab samples using highly sensitive HA- and NA-protein arrays to test the hypotheses that shedding in exhaled fine particle aerosols is negatively associated with mucosal antibody against the influenza virus with which the subject is infected, but positively associated with immunity to related strains in the absence of specific high-level immunity to the infecting strain, and that divergence of upper and lower respiratory tract viral sequences is associated with a high ratio of IgG to IgA immunity to closely related viruses; 3.Identify co-infection using a TaqMan® Array Card assay to test the hypothesis that aerosol shedding is associated with co-infection, controlled for other host factors (including BMI, sex, cough frequency, vaccination, mucosal immunity, symptoms, asthma, smoking, and viral load as measured in NP swabs). Integrate the analysis of sequence data, mucosal immunity, and co-infection and incorporate data from the DARPA-BARDA Prometheus Years 1-3 (2017-19). Non-Severable Option 20E Emerging Pathogen Project: 0258-0686-4609 This option represents partial funding of a continuing COVID-19 surveillance and exhaled breath aerosol assessment study, designed to be carried out over a period of 3 months. The recipient shall: 1. Recruit COVID-19 cases through three mechanisms: 1) Surveillance of an at-risk cohort via daily symptom checks and weekly PCR testing; 2) Direct recruiting of cases through the Prince George's County health department and local providers including the UMD University Health Center; and 3) Intensive surveillance of household contacts of cases identified from the atrisk cohort and referred cases. The recipient shall aim to recruit at least 12 cases per month (36 or more total over the period of performance) and at least 44 or more total household contacts. 2. Obtain mucosal swabs, blood (sera and PBMCs), saliva from COVID-19 cases. 3. Obtain exhaled breath samples from COVID-19 cases, via the Gesundheit-II bioaerosol sampler including paired back-to-back samples from each case wearing a) a face mask or face shield, and b) no face mask or shield, and/or a) without loud talking or singing and b) with loud talking or singing, on at least two separate days. 4. Test saliva, swabs, and exhaled breath samples for SARS-CoV-2 using the Thermo-Fisher TaqPath assay in a 96-well format in a QuantStudio 7, and quantitate RNA copy numbers in positive samples. 5. Culture positive samples for virus through the services of Matthew Frieman's BSL-3 lab at the University of Maryland School of Medicine in Baltimore. 6. Analyze qRT-PCR and culture analysis results to test the hypotheses a) that asymptomatic and minimally symptomatic infections shed infectious aerosols; b) that a small fraction of cases shed the vast majority of viral aerosols; and c) that surgical and homemade face masks but not face shields are effective source control. 7. Maintain a biorepository of these samples.
University Of Maryland, College Park
Definitive Contract HHSN272201400008C
$1.1m 9/23/20 025806564612S
Yr.19-20: 0258-0656-4612 Yr.20-21: 0258-0676-4612 Nasopharyngeal aspirates will be collected from children enrolled in the Umoya cohort at Tyberberg Hospital in Cape Town, South Africa. All influenza positive samples will be sent the Shaw laboratory at the University of the Western Cape. RNA will be extracted from each sample and influenza cDNA will be amplified, then sent to the van Bakel laboratory at Icahn School of Medicine at Mount Sinai for full next generation sequencing. Virus will also be cultured from each sample by amplification in MDCK cells, and viral stocks will be produced. Each virus stock will be verified by full sequencing and characterized in terms of sub-type, growth properties, and susceptibility to approved influenza drugs. The antigenic relatedness to viruses in the current vaccine will also be investigated. Finally, we will compare the baseline sequence data obtained from the initial sample with the sequence of the cultured virus, and assess the intrinsic sequence diversity of the influenza virus population in each clinical sample. All sequence data will be sent to the CEIRS Data Processing and Coordinating Center for dissemination to public databases.
University Of The Western Cape
Definitive Contract HHSN272201400008C
$293.1k 10/28/19 025806444612S
Influenza viruses cause recurrent epidemics of febrile respiratory disease every year. The influenza impact is reduced by yearly administration of seasonal influenza vaccines, which has to be reformulated every year due to the changes in the influenza viruses. The main objectives of this study are to obtain pre- and post- influenza vaccination human sera from outpatients and healthy volunteers vaccinated with the Northern Hemisphere QIV influenza vaccine to evaluate vaccine effectiveness, measured as seroconversion, and antigenic characterization of circulating seasonal influenza strains for WHO vaccine virus selection decision-making process.
Fundacion Para La Gestion De La Investigacion En Salud De Sevilla
Definitive Contract HHSN272201400008C
$57.2k 5/15/19 025806404609S
Non-Severable Option 19C Pathogenesis Project Cross-reactive lung resident memory T cells during experimental human influenza infection and their similarity to mouse Recent evidence from mouse models has shown that T-cells (in particular resident memory T (Trm) cells in the lung) can protect against influenza infection and disease as well as conferring cross-strain protection. However, since systematic sampling of T-cells from the respiratory tract is practically impossible in infected patients, there is little understanding of how lung-resident T-cells are generated during influenza infection and whether they contribute to preventing severe disease in humans as in mice. Aims 1. Challenge 10 individuals with influenza A/Belgium/4219/15 (H3N2) to define the heterogeneity of clinical, virological and immunological outcomes before, during and after infection. a. Identify novel combinations of markers that define subsets of lung resident T cells by mass cytometry and their changes over influenza infection b. Using pools of conserved immunodominant T cell epitopes and intracellular cytokines staining, quantify the frequencies of antigen-specific memory T cells in the human airway 2. Analyze by Meso-Scale Discovery soluble mediators in the lower airway 3. Discover surrogate biomarkers in the nose and blood that correlate with Trm cells in the lung. Compare T cell responses in the human challenge model with data from murine models. 4. Optimize sampling and processing methods in preparation for a larger follow-up study to investigate Trm cell generation by analyzing lower airway T cells, bronchial fluids and tissues using a systems biology approach. To test the concordance of Trm cell responses in the animal model with humans, we will challenge 10 healthy adult individuals with influenza A/Belgium/4219/2015, a recent seasonal H3N2 strain provided as an in-kind contribution by SGS. Ethical approval is in place (London-Fulham NRES committee reference 11/LO/1826). Currently, only one other academic institution in the world conducts controlled human influenza infection, while sampling and investigation of lower airways cells and tissues in this context are unique to our group. Individuals with strain-specific antibody titres 75% in previous studies with this challenge virus. Volunteers will therefore be screened to select for low MN titers and using established inclusion/exclusion criteria. Blood, nasal and bronchial samples will be taken prior to inoculation. Around 2 weeks later, subjects will be inoculated intranasally. Post-inoculation, subjects will be confined to an isolation facility for up to 10 days to avoid onward transmission and for daily sampling (Table 1). Following discharge, they will be reviewed on day 14, 28 and 6 months for repeat sampling and assessment of immune memory. Further bronchoscopies will be performed on day 7, 28 and 180 post-inoculation. Antigen-specific T-cells will be characterized phenotypically and functionally. T-cells from blood and BAL of influenza-infected volunteers will be analyzed by mass cytometry (CyTOF) for discovery of previously unrecognized Trm cell markers with more focused analysis by flow cytometry. Cytotoxicity, cytokine-production, degranulation and proliferative capacity will be assessed using established methods. From the lower airways, we will collect bronchial lining and BAL fluid for multiplex cytokine analysis by Meso-Scale Discovery. Bronchial brushings and biopsies will additionally be stored for future analysis by transcriptomics. Quantitative, phenotypic and functional analyses of lower airway T cells and soluble mediator levels will be correlated with responses in blood and nose to identify markers that correlate with lower airway responses. Data from previous human challenge studies with influenza A(H1N1)2009 and respiratory syncytial virus; and murine influenza-specific Trm cell models generated at
Imperial College Of Science, Technology And Medicine
Definitive Contract HHSN272201400008C
$236.9k 2/19/19