10000 documents

Interplay between coronaviruses and nonsense-mediated mRNA decay pathway

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

Shinji Makino · UNIVERSITY OF TEXAS MED BR GALVESTON · 2020 · $309,206 — Coronaviruses (CoVs), which carry a large, single-stranded, positive-sense RNA genome, cause a variety of diseases in humans and domestic animals. Human CoVs (HCoVs) usually infect the respiratory tract and cause a range of symptoms varying from mild, such as the common cold, to more serious respira…

Design and testing of germline-targeting and boosting immunogens to elicit 10E8-like broadly neutralizing antibodies against HIV

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

WILLIAM R. SCHIEF · SCRIPPS RESEARCH INSTITUTE, THE · 2020 · $911,231 — Induction of broadly neutralizing antibodies (bnAbs) is a critical unmet goal of HIV vaccine development. BnAb 10E8 is of particular interest as a vaccine lead due to its (1) very high breadth, (2) low number of mutations required to develop broad neutralization, (3) low auto-reactivity, (4) expe…

Transcriptional and functional profiling of cross-reactive T cells to understand outcomes for the pathogen and host during heterologous infection

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

Mariah A Hassert · SAINT LOUIS UNIVERSITY · 2020 · $30,773 — Zika virus (ZIKV) spread explosively throughout the Americas in 2015, leaving in its wake a devastating and ever-expanding list of sequela associated with infection. Since this epidemic, substantial effort has been put forth to understand the emergence of ZIKV in the Americas, the course of disease …

Development of superior polymerases for next-generation mRNA therapeutic & vaccine manufacturing

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

Helge Zieler · PRIMROSE BIO, INC. · 2020 · $1,152,047 — Project Summary/Abstract Messenger ribonucleic acid (mRNA) plays key roles in cells and organisms as a carrier of protein-coding information and as a regulator of gene expression. The pharmaceutical industry has begun to exploit the many natural functions of mRNA to develop novel therapeutics and v…

Systems Biology of Mumps Vaccine Response

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

Richard B Kennedy · MAYO CLINIC ROCHESTER · 2020 · $786,112 — PROJECT SUMMARY/ABSTRACT This application is a request for funding of a research program focused on understanding the factors associated with waning immune response to mumps vaccine. Waning immunity to mumps is a public health concern and a major obstacle in the control and elimination of mumps dise…

RNA Metabolism in Trypanosomes

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

CHRISTIAN TSCHUDI · YALE UNIVERSITY · 2020 · $751,764 —  DESCRIPTION (provided by applicant): This application focuses on the protozoan parasite Trypanosoma brucei, which causes devastating diseases in humans and animals in sub-Saharan Africa. There are no vaccines, and therapeutic drugs have serious side effects and decreasing efficacy. Thus, there …

Epitope-Based Design and Modified RNA Platform for Bivalent Marburgvirus Vaccine

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

Alexander Bukreyev · UNIVERSITY OF TEXAS MED BR GALVESTON · 2020 · $769,175 — PROJECT SUMMARY/ABSTRACT The Marburg virus (MARV) and Ravn virus (RAVV), which both belong to the genus Marburgvirus of the family Filoviridae, cause the severe disease in humans, with case fatality rates up to 90%. There are no licensed vaccines against marburgviruses. Clinical trials of vaccine ca…

Evaluating Companion Diagnostics to the anal Pap test to improve prediction of AIN2+ in HIV-infected MSM

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

JEANNE ANN JORDAN · GEORGE WASHINGTON UNIVERSITY · 2020 · $577,224 — ABSTRACT Human papillomavirus (HPV) infections are highly prevalent in men and women. High-risk (HR) HPV types 16 & 18 (HPV16/18) are responsible for ~90% of all anal cancers, whose incidence has risen by 96% in the last 2- 3 decades primarily because of the HIV/AIDS epidemic. Indeed, HIV-infected m…

RNA Selection in the Packaging of Segmented dsRNA Viruses

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

John Thomas Patton · TRUSTEES OF INDIANA UNIVERSITY · 2020 · $189,934 — Rotaviruses, a large and genetically diverse group of segmented double-stranded (ds)RNA viruses, are a significant cause of gastroenteritis in many mammalian and avian species. Among infants and young children, rotavirus infections can result in life-threatening dehydrating diarrheal disease. Like o…

Messenger RNA capping and methylation in pneumoviruses

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

Jianrong Li · OHIO STATE UNIVERSITY · 2020 · $469,725 — Abstract This application is to renew a grant to study RNA methylation in pneumoviruses. Pneumoviridae is a new virus family, created in 2016 by elevating the paramyxoviral subfamily Pneumovirinae to family status. The Pneumoviridae family includes two medically important pathogens, human respirator…

CD4 T cell control of cytomegalovirus

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

CHRISTOPHER A BENEDICT · LA JOLLA INSTITUTE FOR IMMUNOLOGY · 2020 · $720,659 — Summary Cytomegalovirus (CMV, a b-herpesvirus) establishes a persistent infection that is endemic in humans and mice. CMV causes acute clinical disease only if immunity is naïve or compromised, exemplifying how coevolution with its host over millennia has resulted in a largely non-pathogenic détente…

The Roles of Lymphoid Tissue Microenvironments in Guiding the Immune Response

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

Michael Gerner · UNIVERSITY OF WASHINGTON · 2020 · $478,512 — The innate and adaptive arms of the immune system are integrally linked, with dendritic cells (DCs), innate antigen presenting cells, providing critical instructions to elicit the generation of adaptive T cell immunity. Using a novel analytical imaging approach, we recently uncovered that different …

Role of SIV and HIV Env cytoplasmic tail in pathogenesis and protective immunity

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

James A Hoxie · UNIVERSITY OF PENNSYLVANIA · 2020 · $752,353 — Project Summary In pathogenic HIV and SIV infection innate and adaptive immune responses fail to control viral replication and, coupled with persisting immune activation, lead to the progressive depletion of CD4+/CCR5+ T cells and AIDS. Numerous HIV and SIV vaccines have also failed to elicit immune…

Lipid nanoparticles as novel adjuvants inducing effective T follicular helper cell and humoral immune responses

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

Norbert Pardi · UNIVERSITY OF PENNSYLVANIA · 2020 · $622,103 — ABSTRACT Vaccines prevent hundreds of millions of illnesses and save millions of lives every year. Various types of licensed vaccines (live attenuated and inactivated pathogens, adjuvanted protein subunits) provide some level of protection against a variety of dangerous illnesses. However, there are…

New Materials to Deliver mRNA: Applications in Cancer Immunotherapy

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

RONALD LEVY · STANFORD UNIVERSITY · 2020 · $546,613 — Project Summary: Cancer is a leading global cause of mortality. The goal of this multi-disciplinary project is to pre-clinically advance a novel concept for selective and efficient mRNA delivery that enables a highly promising vaccination strategy for cancer immunotherapy. Given the potential of can…

Mechanism of Flavivirus RNA Capping

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

Brian Geiss · COLORADO STATE UNIVERSITY · 2020 · $374,993 — Approximately 2/3rd of the world population is at risk of infection by at least one of the 35 insect-borne flaviviruses known to cause disease in humans. There are currently few vaccines and no therapeutics available to treat patients infected by flaviviruses such as Dengue, Zika, and West Nile viru…

Messenger RNA Immunogens for initiation of protective HIV non-neutralizing antibodies

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

Barton F. Haynes · DUKE UNIVERSITY · 2020 · $3,798,808 — While HIV-1 broadly neutralizing antibodies (bnAbs) provide potent protection from HIV-1, to date they have been difficult to induce in the setting of vaccination. A second type of HIV-1 envelope (Env) antibodies that are easy to induce are termed non-neutralizing antibodies (NNAbs) (because they ar…

Pulmonary Innate Immunity & Resistance to Mycobacterium Tuberculosis Infection

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

Thomas R Hawn · UNIVERSITY OF WASHINGTON · 2020 · $178,442 — Despite the discovery of Mycobacterium tuberculosis (Mtb) over 100 years ago and the availability of effective drugs for over 60 years, there remain formidable hurdles for controlling tuberculosis (TB) disease including the lack of a highly efficacious vaccine, long drug treatment regimens, preventi…

Mechanistic Exploration of cGAS-STING-Mediated Vaccine Enhancement

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

VICTOR Robert DEFILIPPIS · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $640,563 — PROJECT SUMMARY The goals of this R01 proposal include the molecular and immunological characterization of vaccine adjuvant activity associated with processes mediated by the protein Stimulator of Interferon Genes (STING). Two vital insufficiencies are currently evident regarding adjuvanted human va…

Developing a Screen for New Adjuvants to Enhance RNA Vaccines

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

DARRICK Albert CARTER · PAI LIFE SCIENCES, INC. · 2020 · $290,045 — PROJECT SUMMARY RNA vaccines are a growing area of interest in vaccinology. They are flexible in that the purification process should be similar from one vaccine to the other and that they can be rapidly made in response to emerging diseases. Use of these nucleic acid constructs as a vaccine platfor…