Translational Research Toward Development of a Kaposi Sarcoma Herpesvirus (KSHV) Vaccine (U01 Clinical Trial Optional) | RFA CA 24 006

Opportunity Information: Apply for RFA CA 24 006

This funding opportunity (RFA-CA-24-006) is a National Institutes of Health initiative led by the National Cancer Institute to push Kaposi sarcoma herpesvirus (KSHV) vaccine research from foundational discoveries into the kinds of applied, translational work that can produce real vaccine candidates and the evidence needed to move them forward. The NOFO explicitly builds on earlier NCI-supported efforts focused on understanding how KSHV is transmitted (RFA-CA-18-013 and RFA-CA-20-046). The goal now is to leverage what has been learned about transmission and early infection to guide the development of either a prophylactic vaccine (to prevent infection in the first place) or a therapeutic vaccine (to help people already infected control infection or reduce disease).

The public health and cancer relevance is central to the program. KSHV is the cause of Kaposi sarcoma (KS) and is also linked to other serious KSHV-associated diseases and syndromes, including multicentric Castleman disease (MCD), primary effusion lymphoma (PEL), and KSHV inflammatory cytokine syndrome (KICS). A prophylactic vaccine is framed as a way to prevent primary infection, reduce person-to-person spread, and ultimately prevent downstream cancers and inflammatory syndromes associated with the virus, or at least lessen disease severity. A therapeutic vaccine is positioned as potentially beneficial for people already living with KSHV by preventing progression, recurrence, or complications of KSHV-associated disease.

The NOFO highlights several broad scientific areas where applicants can propose projects, with flexibility to pursue additional relevant directions. One major emphasis is identifying and evaluating vaccine targets, which can include both structural viral components (for example, proteins present on the virus particle that might be recognized by neutralizing antibodies) and non-structural components (such as proteins expressed during infection that could be useful for T cell-based immunity). Another priority is building and refining animal models suitable for studying KSHV vaccine concepts. Because KSHV biology and disease are challenging to replicate, model development is treated as an important step for testing immunogenicity, protection, and mechanisms, and for comparing different platforms or antigen choices.

The NOFO also supports the direct development and testing of candidate vaccines, meaning projects can cover the pipeline from antigen selection and vaccine design through preclinical evaluation and readiness for further testing. The "Clinical Trial Optional" label indicates that the mechanism allows, but does not require, clinical trial activity; applicants can propose strictly preclinical/translational work or include clinical components if appropriate and justified. Another highlighted area is optimizing vaccine performance for people with HIV (PWH). This reflects the reality that immune status and co-infections can influence vaccine responses and disease risk, and that KSHV-associated conditions are particularly relevant in immunocompromised populations. Projects in this category might examine dosing, adjuvants, schedules, immune correlates, or other strategies to maximize efficacy and durability in PWH.

A further scientific focus is clarifying the earliest steps of KSHV infection and the main modes of person-to-person transmission in different populations, with the practical intent of identifying points that a vaccine could block. This includes understanding how exposure occurs, what tissues or cell types are first infected, and what immune responses are needed at those sites to prevent establishment of infection. Finally, the NOFO calls for optimization and standardization of KSHV detection methods, recognizing that consistent, reliable assays are essential for measuring infection, viral load, immune responses, and endpoints that would be needed to evaluate vaccine candidates across studies and, eventually, in clinical settings.

In terms of award structure, this is a U01 cooperative agreement, which typically means NIH program staff will have substantial involvement in coordinating and guiding the overall program compared with a standard research project grant. The activity areas are in health and education, and the associated CFDA listings are 93.393, 93.395, and 93.399. The original application due date listed is December 4, 2024, and the opportunity was created on October 16, 2023. The posting does not provide an award ceiling or expected number of awards in the excerpt provided, so applicants would need to consult the full NOFO for budget and project period expectations.

Eligibility is broad and includes many types of U.S. organizations and governmental units, such as state, county, city/township, and special district governments; public and state-controlled and private institutions of higher education; independent school districts; public housing authorities/Indian housing authorities; federally recognized tribal governments and other tribal organizations; nonprofits (with and without 501(c)(3) status); for-profit organizations (other than small businesses) as well as small businesses; and additional categories labeled "Other." The NOFO also explicitly encourages or allows participation by a range of mission-driven and historically underrepresented institutions and organizations, including HBCUs, Hispanic-serving institutions, AANAPISI institutions, Alaska Native and Native Hawaiian-serving institutions, tribally controlled colleges and universities, faith-based or community-based organizations, regional organizations, U.S. territories or possessions, and non-U.S. entities (foreign organizations), among others.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Translational Research Toward Development of a Kaposi Sarcoma Herpesvirus (KSHV) Vaccine (U01 Clinical Trial Optional)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.393, 93.395, 93.399.
• This funding opportunity was created on 2023-10-16.
• Applicants must submit their applications by 2024-12-04. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for RFA CA 24 006

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