Rational Design of Vaccines Against Hepatitis C Virus (U19 Clinical Trial Not Allowed)

The National Institutes of Health, through the National Institute of Allergy and Infectious Diseases, is inviting applications for a cooperative research program focused on the rational design of vaccines against the hepatitis C virus. This opportunity aims to establish a consortium of Research Centers that will collectively advance the understanding, design, and preclinical evaluation of broadly protective HCV vaccines. The program emphasizes translational research that bridges structural virology, immunology, and vaccine development, with the goal of generating and optimizing candidates capable of inducing broad neutralizing antibody and T-cell responses suitable for clinical development. This NOFO continues NIH’s long-standing commitment to supporting biomedical research that targets infectious and immunologic diseases with substantial global health burdens. Hepatitis C virus remains a leading cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma worldwide, despite the availability of effective antiviral treatments. Approximately 71 million people are chronically infected globally, including over two million in the United States. Current therapies do not prevent reinfection, and the persistence of underdiagnosis and limited treatment access underscores the urgent need for an effective vaccine. Vaccine development for HCV has been hindered by its complex genetic diversity, high mutation rate, and lack of appropriate animal models. Recent advances in the structural biology of viral envelope glycoproteins and the identification of broadly neutralizing antibodies now provide a foundation for a rational vaccine design approach, making this NOFO both timely and strategically significant. Applicants are expected to form multi-project research centers composed of an Administrative Core, optional Scientific Cores, and at least two integrated Research Projects. These centers will work collaboratively within a national consortium coordinated by NIAID. Each center will be responsible for designing and optimizing HCV vaccine candidates, evaluating immunogenicity in relevant models, and generating data to support future IND-enabling studies. Administrative and Scientific Cores are expected to provide coordination, shared resources, and standardized assay development to ensure reproducibility and cross-comparison of vaccine candidates. Collaboration will be a major component, with annual consortium and progress meetings mandated for all awardees to ensure alignment and knowledge exchange across funded centers. Applications must follow NIH’s multi-project (M) application instructions and be submitted electronically through the ASSIST system or an institutional system-to-system interface linked to Grants.gov. The earliest submission date is October 7, 2025, and full applications are due by November 7, 2025, at 5:00 PM local time of the applicant organization. Applications will undergo peer review in March 2026, advisory council review in May 2026, and selected awards will begin in July 2026. No letters of intent are required, and this opportunity is not subject to Executive Order 12372 intergovernmental review. The announcement expires on November 8, 2025. All applicants must have active registrations in SAM.gov, eRA Commons, and Grants.gov, and principal investigators must maintain eRA Commons credentials. NIAID intends to commit $8.3 million in FY 2026 to fund two to four awards under this opportunity. Each application may request up to $2 million in direct costs per year for a maximum period of five years, reflecting the scope and complexity of proposed vaccine development activities. No cost sharing or matching is required. Foreign organizations and non-domestic components of U.S. institutions are eligible to apply, but NIH will not issue awards that include foreign subawards or subcontracts unless the NOFO explicitly allows international collaborations. Projects may include preclinical and translational research but may not include clinical trials as defined by NIH. Applications will be evaluated on scientific significance, innovation, approach, investigator qualifications, and research environment. Reviewers will also assess plans for data management, human and animal subjects protections, biohazard safety, and resource sharing. Successful centers must demonstrate strong management structures, well-integrated project designs, and clear plans for advancing vaccine candidates toward clinical testing. Contact for scientific and research inquiries is Dr. Rajeev Gautam (gautamr2@mail.nih.gov, 301-761-5347). Financial or grants management questions should be directed to Jackie Verrecchia (jackie.verrecchia@nih.gov, 301-761-6652). This program is authorized under Sections 301 and 405 of the Public Health Service Act and governed by 42 CFR Part 52 and 2 CFR Part 200.

Applicants should submit early to allow corrections before the deadline. NIH emphasizes compliance with the Application Guide. Applications that deviate will be considered non-compliant. Collaborations across projects and strong administrative management are critical