NIAID invites investigators to apply to the New Therapeutic Strategies for Genital Herpes (R21/R33, Clinical Trial Not Allowed) notice of funding opportunity (NOFO) that uses a milestone-driven, phased innovation award to stimulate the development of new or improved antivirals, monoclonal antibodies, and other treatments for people living with the herpes simplex virus (HSV) infection cycle, or genital herpes. The NOFO aligns with the NIH Strategic Plan for HSV Research.
The HSV infection cycle presents challenges in the development of new treatments, which results in suboptimal treatment options. The best available treatments do not eliminate recurrences and only provide a partial reduction of shedding, meaning that the virus can still be transmitted to uninfected partners or to newborns. The most promising current therapeutic options target active virus replication, rendering them ineffective against latent infection.
Research Objectives
The NOFO invites applications focused on developing new candidates or identifying new targets for the treatment of genital herpes, to include:
- Improved antiviral therapeutics (non-nucleoside analogs and improved nucleosides)
- Therapeutic vaccines
- Monoclonal antibodies (mAbs)
- Technologies that target HSV latency (e.g., CRISPR/Cas, meganucleases)
NIAID seeks to capitalize on the robust HSV basic research field and to encourage more researchers to advance products into the development pipeline. There are a number of essential replication proteins encoded by herpes viruses that could serve as novel targets for antiviral therapy, which may include targets such as packaging or budding proteins. Novel therapies could synergize with current treatment regimens to improve activity against recurrent outbreaks and viral shedding, while decreasing the chance of developing resistance.
A therapeutic vaccine also has the potential to serve as a functional cure by possibly reducing reactivation, symptoms, and risk of transmission. Unlike a prophylactic vaccine administered to prevent HSV infection, a therapeutic vaccine would be administered to those who already have HSV, to help suppress symptoms.
Note that applications cannot propose research focused on devices, prophylactic vaccines, or topical treatments; nor can applications lack a milestone section in the R21 phase.
Phased Innovation Awards
Due to the high-risk, high-impact nature of the research, this NOFO will use the R21/R33 Phased Innovation Award activity code. Support will be provided for up to 2 years (R21 phase) for milestone-driven research to develop new therapeutic candidates for the treatment of genital herpes. Up to 3 years of support (R33 phase) may follow the R21 phase for additional activities as appropriate, such as in vivo pharmacokinetics, toxicology, animal efficacy studies, scale-up of the candidate product, or optimizing production. Proposed milestones will be reviewed and negotiated prior to award. No less than 2 months prior to completion of the R21 phase, recipients must submit an R21 progress report describing in detail the progress made towards completion of the R21 milestones. Recipients may be asked to include other information necessary for successful evaluation of the R21 phase of the project.
NIAID program staff will conduct an administrative review of projects nearing completion of the R21 phase and assess readiness to transition to the R33 phase. Awards selected for continued funding will transition to an R33 award without the need to reapply. Transition to the R33 phase is neither automatic nor guaranteed. R33 funding decisions will be based on the original R21/R33 peer review recommendations, successful completion of R21 milestones, program priorities, and availability of funds. We anticipate approximately 50 percent of grants funded in the R21 phase will transition to the R33 phase.
Deadline and Award Information
NIAID plans to fund 7 to 10 awards. Budgets for the R21 phase are limited to $275,000 in direct costs across the 2 years. R33 phase budgets are not expected to exceed $300,000 in annual direct costs for up to 3 years.
All applications are due on January 31, 2025, by 5:00 p.m. local time of the applicant organization.
Contact Information
Send inquiries to NIAID’s scientific/research contacts, Dr. Kristie Connolly at kristie.connolly@nih.gov or 240-669-5572 and Dr. Mindy Davis at mindy.davis@nih.gov or 301-761-6689. Direct any questions about peer review to NIAID’s Dr. Mario Cerritelli at cerritem@mail.nih.gov or 240-669-5199.