Mvacs – mrna vaccines for c. Difficile suppression

Active Cooperative Agreement Awarded Last action

Award ID
U19AI174998
Recipient
Awarding agency
Obligated
$12,086,637

Award facts

Assistance listing
93.855 Allergy and Infectious Diseases Research
Completion date 73% complete
Place of performance
Philadelphia, PA 19104, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Mvacs program clostridioides difficile is the most reported nosocomial pathogen in the united states and a major public health threat worldwide. Challenges in treating infections with conventional antibiotics and increasing rates of recurrent infection underscore the need for new interventions. To date, no vaccine has proven to be effective at clearing c. Difficile from infected individuals. The mvacs program-"mrna vaccines for c. Difficile suppression"-is tightly focused on the goal of designing and implementing improved vaccines to mitigate or eliminate c. Difficile infection (CDI). For this we will employ modified mrna vaccine technology, which has been pioneered so successfully by team member DR. Drew weissman and his collaborators at biontech to immunize against sars- COV-2. Already DRS. Weissman, alameh, and zackular have established a collaboration with biontech to develop an mrna targeting c. Difficile toxins and other antigens and shown their lead formulation to be highly protective in mice challenged with a lethal dose of c. Difficile. However, c. Difficile is not fully cleared from the mice, and there is mild transient pathogenesis, so there is more to be done. The team is moving forward with this anti-toxin vaccine, but improvements in design are necessary for optimal efficacy. The mvacs team is a highly skilled and synergistic group dedicated to developing modified mrnas to oppose c. Difficile infection and pathogenesis. The program consists of three projects and three cores. Project 1 (vaccine development) (project leads: alameh and weissman) will test new mrnas against multiple c. Difficile targets, as well as mixtures of mrnas and novel nanoparticle/lipid formulations. Project 2 (antigen discovery) (project lead: zackular) will take advantage of advanced analysis of c. Difficile microbiology and ecology of infection to produce a series of novel vaccine targets. Project 3 (immunology) (project lead: ABT) will quantify mucosal adaptive immune responses against c. Difficile in humans and mouse systems, identifying gaps and correlates of efficacy. Projects 2 (antigen discovery) and project 3 (immunology) will flow new data to project 1 (vaccine development) to optimize vaccine design. The projects will be complemented by three cores: core a (administrative core) (core leads: bushman and weissman), core b (genomics core) (core leads: bittinger, bushman, and moustafa) and core c (clinical core) (core leads: kelly and conrad). Together with our industry partner biontech, we are highly optimistic that we can advance effective new vaccine designs to suppress c. Difficile.

Transactions

Action Obligated Date
Amendment $1,529,954
Amendment $1,529,954
Amendment $152,995
Amendment $152,995
Amendment $1,376,959
Amendment $1,376,959
Amendment $1,376,959
Amendment $1,529,954
Amendment $1,529,954
Original award $1,529,954

Subawards

Subrecipient Amount Awarded
The Children's Hospital Of Philadelphia The Alameh Lab will be mainly responsible in collaboration with Dr Weissman and researchers from Project 2 and 3 for the development of the mRNA vaccine against… $245,302
University Of North Carolina Hospitals At Chapel Hill Work for Project 3 entails quantification of phase variation by C. difficile during infection. $35,927
The Children's Hospital Of Philadelphia "Dr. Bittinger directs the Analytical Laboratory for the CHOP Microbiome Center. He will lead the bioinformatics analysis of the metagenomic and… $65,107
The Children's Hospital Of Philadelphia "Clostridioides difficile is a spore-forming pathogen that causes a wide range of gastrointestinal (GI) disorders varying in severity from mild diarrhea to… $319,306
University Of North Carolina Hospitals At Chapel Hill "will oversee aspects of the project related to C. difficile phase variation. Work for Project 2 involves determining the extent of heterogeneity in… $63,329
University Of Florida "Dr. Prentice will oversee the proposed IMS work including supervising and training personnel, procurement, performing experiments, data analysis, and aiding in… $63,536
The Children's Hospital Of Philadelphia The Alameh Lab will be mainly responsible in collaboration with Dr Weissman and researchers from Project 2 and 3 for the development of the mRNA vaccine against… $245,302
The Children's Hospital Of Philadelphia "Objective: C. difficile is the most commonly reported nosocomial pathogen in the United States and a major public health threat worldwide. Over the past… $61,511
The Children's Hospital Of Philadelphia "Clostridioides difficile is a spore-forming pathogen that causes a wide range of gastrointestinal (GI) disorders varying in severity from mild diarrhea to… $250,515
University Of North Carolina Hospitals At Chapel Hill Work for Project 3 entails quantification of phase variation by C. difficile during infection. $35,927
The Children's Hospital Of Philadelphia "Dr. Bittinger directs the Analytical Laboratory for the CHOP Microbiome Center. He will lead the bioinformatics analysis of the metagenomic and… $65,875
University Of Florida "Dr. Prentice will oversee the proposed IMS work including supervising and training personnel, procurement, performing experiments, data analysis, and aiding in… $62,905
University Of North Carolina Hospitals At Chapel Hill "will oversee aspects of the project related to C. difficile phase variation. Work for Project 2 involves determining the extent of heterogeneity in… $63,462
The Children's Hospital Of Philadelphia The Alameh Lab will be mainly responsible in collaboration with Dr Weissman and researchers from Project 2 and 3 for the development of the mRNA vaccine against… $238,360
The Children's Hospital Of Philadelphia Clostridioides difficile is a spore-forming pathogen that causes a wide range of gastrointestinal (GI) disorders varying in severity from mild diarrhea to… $248,530
University Of Florida Dr. Prentice will oversee the proposed IMS work including supervising and training personnel, procurement, performing experiments, data analysis, and aiding… $37,212
The Children's Hospital Of Philadelphia Focus is on how the mucosal immune system regulates commensal microbial communities. Expertise in microbial flow sorting and sequencing will be used for… $43,340
The Children's Hospital Of Philadelphia Scope of work: Conventional animals: Funds are requested for the purchase of mice for vaccine challenge experimentation described in Project 1. Each animal will… $25,961
The Children's Hospital Of Philadelphia Dr. Bittinger directs the Analytical Laboratory for the CHOP Microbiome Center. He will lead the bioinformatics analysis of the metagenomic and… $60,907
The Children's Hospital Of Philadelphia Objective: C. difficile is the most commonly reported nosocomial pathogen in the United States and a major public health threat worldwide. Over the past decade,… $61,511
University Of North Carolina Hospitals At Chapel Hill will oversee aspects of the project related to C. difficile phase variation. Work for Project 2 involves determining the extent of heterogeneity in expression… $56,930
University Of North Carolina Hospitals At Chapel Hill Work for Project 3 entails quantification of phase variation by C. difficile during infection. $32,229
Show all 22

Quick answers

Who received award U19AI174998?

U19AI174998 was awarded to The Trustees Of The University Of Pennsylvania by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on March 1, 2023.

How much is award U19AI174998 worth?

$12,086,637 has been obligated on U19AI174998.

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