Apply for Research Funds To Address CDI Immunity and Vaccine Development

Funding News Edition: February 02, 2022
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NIAID seeks applications for the formation of Cooperative Research Centers (CRCs) to pursue vaccine development through the study of host immune responses to Clostridioides difficile infection (CDI) and by leveraging clinical samples, identifying new protective antigens, and employing novel vaccine and adjuvant platforms. Interested program investigators should apply to join the network through a new funding opportunity announcement (FOA): Host Immunity and Novel Immunization Strategies for Clostridioides difficile Infection (CDI) (U19, Clinical Trial Not Allowed).

Research Objectives and Scope  

CDI is listed as an Urgent Threat in CDC’s 2019 Antibiotic Resistance Threats in the United States report and is the most common healthcare-associated infection in the United States. Despite declining CDI rates and new, innovative treatments, the disease burden has still not been fully addressed. While most individuals have some detectable antibodies against C. difficile, antibody levels tend to wane with advanced age (>65 years), which increases risk for recurrent CDI (rCDI). Additionally, individuals who have taken antibiotics and been hospitalized are also at risk for CDI.

The purpose of this initiative is to support vaccine development that is suitable for use in the target population, provides broad protection from primary infection, prevents deleterious gastrointestinal colonization, and possesses therapeutic potential to break the cycle of rCDI. This research initiative also invites cutting-edge research focused on the impact of the gut microbiome on host adaptive immunity to CDI.

Responsive Areas of Research Interest

NIAID is interested in the following potential areas of research interest for the CRC program:

  • Advance the knowledge of immunological protection against CDI
    • Evaluate the breadth, diversity, and neutralizing capacity of antibodies (antitoxin) from high-risk and other relevant at-risk patient populations
    • Leverage clinical samples to investigate correlates of protection and aspects of immunological memory that influence protective immunity
    • Investigate the impact of the host microbiota on vaccine-induced immunity
    • Investigate key knowledge gaps, such as the role of mucosal or local immunity and the potential to reduce colonization
    • Investigate the role of cellular immunity in protection against CDI
  • Conduct new research on microbial pathogenesis considered important for broadly protective host immunity
    • Explore the impact of antigenic variation on host protective immunity to C. difficile
    • Investigate aspects of C. difficile pathogenesis and life cycle (spore vs. vegetative) that could lead to the discovery of novel protective antigens
  • Application of preclinical models, vaccine platforms, and novel adjuvants
    • Construct prototypic preclinical candidate vaccines designed to test new and existing vaccine targets that have the potential to impact colonization with C. difficile
    • Study preclinical vaccine candidates in animal models that parallel the pathophysiology of the disease
    • Leverage new microphysiological systems (e.g., organoids) that include key components of the host immune system for vaccine testing
    • Use novel vaccine platforms (e.g., mRNA) and adjuvant technology focused on stimulating mucosal immunity in the gut and examine the interplay of host immunity and gut microbiome
  • Develop new animal models to conduct pertinent translational studies to evaluate immunogenicity and correlates of protection
    • Preclinical models that parallel the pathophysiology of human disease (e.g., >65 years, humanized microbiota)

This FOA provides a list of nonresponsive criteria that if included will cause NIAID to not review your application. Additionally, we will consider nonresponsive and not review any applications that do not include milestones and timelines for the overall program component.

Submission and Contact Information

Applications are due on May 20, 2022, by 5:00 p.m. local time of the applicant organization.

Applicant budgets are not to exceed $1 million in annual direct costs and the scope of the proposed project should determine the project period, which should not exceed five years.

Direct your inquiries about this initiative to NIAID’s scientific/research contact, Dr. Ryan Ranallo at 240-627-3351 or If you have questions about peer review for this opportunity, contact Dr. Maryam Feili-Hariri at 240-669-5026 or

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