10000 documents

Administrative Supplement to R21: Mechanism and in vivo activity of novel glycan-based therapy against flavivirus endothelial permeability and vascular leak

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Eva Harris · UNIVERSITY OF CALIFORNIA BERKELEY · 2021 · $207,743 — Supplement to R21: Mechanism and in vivo activity of novel glycan-based therapy against flavivirus endothelial permeability and vascular leak Evaluation of therapeutics targeting SARS-CoV-2 infection and defining pathogenic mechanisms of SARS-CoV-2-triggered pulmonary dysfunction Abstract The emergi…

Defining humoral correlates of immunity against COVID-19

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Galit Alter · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $355,594 — Since 2002, several coronaviruses have emerged able to cause severe respiratory disease, however no vaccine is available to prevent these rapidly spreading pathogens. Vaccine design has specifically lagged due to our lack of understanding of the correlates of immunity against these pathogens. Both c…

University of Pittsburgh Clinical and Translational Science Institute

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

STEVEN E REIS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $976,487 — ABSTRACT The pandemic prompted by the novel SARS-COV-2 virus continues to have a devastating effect on the physical, social, and economic health of communities throughout the world. To evaluate the sero-prevalence of immunity against SARS-COV-2 in the United States, this scientific partnership of Cl…

TMPRSS2 as a potential target for treatments of COVID-19 and respiratory infectious viruses in lung

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Ya-Wen Chen · UNIVERSITY OF SOUTHERN CALIFORNIA · 2021 · $421,219 — Project Summary In December of 2019, a novel coronavirus, now referred to as severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2), struck Wuhan, China and unleashed the current coronavirus disease (COVID-19) pandemic. There are currently no medications or vaccines proven to be effective fo…

Comprehensive profiling of SARS-CoV-2 antibody responses and escape pathways

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

JULIE M. OVERBAUGH · FRED HUTCHINSON CANCER RESEARCH CENTER · 2021 · $489,662 — The ongoing global pandemic of the novel SARS-CoV-2 coronavirus (CoV) presents an urgent need for development of effective preventative and treatment therapies. The viral-host cell fusion (S) protein spike is a prime target for such therapies owing to its critical role in the virus lifecycle. The S …

Novel antibody polymer reagents for SARS-CoV-2 detection

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Lovick Edward Cannon · NOVAB, INC. · 2021 · $256,506 — PROJECT SUMMARY There is an urgent need to rapidly detect SARS-CoV-2 (CoV-2) virus in clinical and nonclinical settings, including point of care sites, workplace, and home, at sensitivity and specificity comparable or superior to RT-PCR detection of CoV-2 RNA. Much of the person-to-person CoV-2 tran…

Structure-function studies of the membrane-interacting domains of HIV-1 Env spike

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

JAMES Jeiwen CHOU · BOSTON CHILDREN'S HOSPITAL · 2021 · $834,248 — Project Summary The first critical step for enveloped viruses, such as HIV-1, to enter host cells is viral membrane fusion. Viral fusion proteins are fascinating protein folding machineries capable of adopting completely different conformations during the fusion process; they are also important vac…

Hyperexcitability in Alzheimer's Disease

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Helen E Scharfman · NATHAN S. KLINE INSTITUTE FOR PSYCH RES · 2021 · $404,250 — ABSTRACT It has been suggested that neuronal hyperexcitability is an important characteristic in Alzheimer’s disease (AD) because it contributes to the impairment in memory and increasing levels of amyloid β (Aβ) that characterize the disease. Using animal models of AD neuropathology we suggest tha…

Recombinant Virus Vaccines

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Bernard Moss · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2021 · $1,846,692 — There are many diseases for which there are no vaccines and others for which the vaccines are not optimal or have significant side effects. The objectives of this project are to develop new vectors, characterize viral antigens, determine targets of humoral and cell mediated immunity, and use this i…

Inhibition of coronavirus release and mitigate COVID-19 pathogenesis

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

PETER D. SUN · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2021 · $158,373 — To characterize the SARS-CoV-2 spike protein interaction with lectin receptors, we have expressed recombinant SARS-CoV-2 spike prefusion trimer using 293F freestyle expression system. Given the nanomolar high affinity of the spike protein binding to human ACE2, the entry receptor for SARS-CoV-2, an…

SARS-CoV2 Immunity and Cell Biology

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Jonathan W Yewdell · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2021 · $23,208 — We have generated Sleeping Beauty transposase vectors that drive expression of the SARS-CoV-2 receptor ACE2 and or protease TMPRSS2 in host cells and use these vectors to create permanent transfected lines of A549, 293FT, and BHK-21 cells. We have generated a recombinant vesicular stomatitis virus t…

Development of a SARS-CoV-2 vaccine

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Bernard Moss · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2021 · $34,549 — We constructed a panel of recombinant MVAs that express unmodified or modified SARS-CoV-2 spike (S) protein. Intramuscular injection of mice with the rMVAs induced antibodies, which neutralized a pseudovirus in vitro and upon passive transfer protected hACE2 transgenic mice from lethal infection wit…

Development of Brain MRI Contrast Agents

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Alan Koretsky · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · 2021 · $1,445,351 — We have made substantial progress towards Aims 1-5, 7&8. Specifically: a) We have reproducibly fabricated 3 nm iron oxide nanoparticles independently in our own lab. These serve as good T1 MRI contrast agents and have strong T2 contrast properties as well. b) We have developed several camelid VHH a…

Design Of Immunogens

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Peter D Kwong · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2021 · $2,127,279 — Based on our understanding of spike- or envelope-based mechanisms of humoral evasion, we are working to design envelope-based immunogens with these evading mechanisms disabled. Such modified immunogens with weakened defenses may elicit more broadly neutralizing antibodies. We have also devised prote…

Epitope dynamics of SARS-CoV-2 S protein by cryo-electron tomography and single particle cryo-EM

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

William Copeland · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · 2021 · $782,795 — We have established high-throughput structure determination workflows using single particle analysis cryo-EM (SPA). These workflows can solve the structure of macromolecular complexes at near atomic resolution in less than 24 hours. In collaboration with Dr. Robert Petrovich at the Protein Expressio…

Epigenetic and environmental factors of ACE2 and TMPRSS2 co-expression

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Joseph Rodriguez · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · 2021 · $443,441 — Viruses use host components for their entire life cycle, from transcription and RNA processing of viral components to export and reinfection of new cells. ACE2 is an estrogen responsive cell receptor used by COVID19 to dock and enter host cells. TMPRSS2 is also an estrogen and androgen responsive …

Characterization of the Pathogenesis of Lymphangioleiomyomatosis (LAM)

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Joel Moss · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · 2021 · $2,633,037 — A.Clinical and molecular effects of mTOR inhibitors: Patients with LAM and TSC are frequently treated with oral mTOR inhibitors. Sirolimus therapy of patients with LAM and TSC resulted in shrinkage of AMLs and stabilization of lung function, but discontinuation of sirolimus led to reversal of these …

Screening for regulators of SARS CoV-2 infection and inflammation

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Iain Fraser · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2021 · $38,806 — Cells of the innate immune system, such as dendritic cells and macrophages, constantly patrol host mucosal surfaces and peripheral tissues for signs of infection or injury. Since many people infected with SARS-CoV-2 clear the virus without developing symptoms, aspects of the innate immune response m…

Paramyxoviruses as Vaccine Vectors Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Ursula Buchholz · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2021 · $698,609 — We are developing paramyxovirus vectored vaccines for intranasal immunization against SARS-CoV-2. These vectors express immunogenic versions of the SARS-CoV-2 S protein and are designed to be highly attenuated in humans while maintaining a high level of immunogenicity at the primary sites of infecti…

Longitudinal IFN signature response and cytokine profiling in patients with severe COVID infections

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Raphaela Goldbach-Mansky · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2021 · $35,545 — In collaboration with the NIAID COVID consortium we have analyzed longitudinally collected whole blood samples collected for RNA isolation from 84 adult patients hospitalized with severe COVID. We also assessed serum samples from a larger panel of adult patients hospitalized with severe COVID (from …