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

FAQs: NIH/NCI KSHV Vaccine Research (RFA-CA-24-006)

1) What is RFA-CA-24-006?

RFA-CA-24-006 is a National Institutes of Health (NIH) funding opportunity led by the National Cancer Institute (NCI) focused on advancing Kaposi sarcoma herpesvirus (KSHV) vaccine research from foundational discoveries into applied, translational work aimed at producing real vaccine candidates and the supporting evidence needed to move them forward.

2) What is the main goal of this funding opportunity?

The main goal is to leverage what has been learned about KSHV transmission and early infection to guide development of either a prophylactic vaccine (to prevent infection) or a therapeutic vaccine (to help people already infected control infection or reduce disease), moving the field toward viable vaccine candidates and measurable endpoints for future evaluation.

3) Why is KSHV vaccine research a public health and cancer priority?

KSHV causes Kaposi sarcoma (KS) and is 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 vaccine could reduce primary infection, limit person-to-person spread, and ultimately prevent downstream cancers and inflammatory syndromes associated with KSHV or lessen disease severity.

4) What types of vaccines are supported: prophylactic, therapeutic, or both?

Both are supported. The opportunity specifically describes development paths for prophylactic vaccines (aimed at preventing primary infection and reducing transmission) and therapeutic vaccines (aimed at benefiting people already living with KSHV by preventing progression, recurrence, or complications of KSHV-associated disease).

5) How does this NOFO relate to prior NCI-supported KSHV work?

This NOFO explicitly builds on earlier NCI-supported efforts that focused on understanding how KSHV is transmitted (RFA-CA-18-013 and RFA-CA-20-046). The current emphasis is to use those transmission and early-infection insights to drive translational vaccine development.

6) What research areas does the NOFO encourage?

The NOFO highlights several broad and flexible scientific areas, including: (a) identifying and evaluating vaccine targets; (b) building and refining animal models suitable for studying KSHV vaccine concepts; (c) direct development and testing of candidate vaccines from design through preclinical evaluation; (d) optimizing vaccine performance for people with HIV (PWH); (e) clarifying earliest steps of infection and transmission modes across populations; and (f) optimizing and standardizing KSHV detection methods and assays for consistent measurement across studies.

7) What does "identifying and evaluating vaccine targets" mean in this NOFO?

It refers to finding and assessing viral components that could be used as antigens in a vaccine. The NOFO notes that targets can include structural viral components (such as proteins 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).

8) Are non-structural viral targets allowed, or only targets on the virus particle?

Non-structural targets are explicitly included. The NOFO describes both structural components (often tied to neutralizing antibody responses) and non-structural components (often tied to T cell-based immunity) as valid directions for target discovery and evaluation.

9) Why is animal model development emphasized?

KSHV biology and disease are challenging to replicate, so developing and refining animal models is treated as an important step for testing immunogenicity, protection, and mechanisms, and for comparing different vaccine platforms or antigen choices.

10) Does this opportunity support direct vaccine candidate development and testing?

Yes. The NOFO supports direct development and testing of candidate vaccines, including work spanning antigen selection, vaccine design, preclinical evaluation, and readiness for further testing.

11) Are clinical trials required under this NOFO?

No. The NOFO is labeled "Clinical Trial Optional," meaning the mechanism allows (but does not require) clinical trial activity. Applicants can propose strictly preclinical/translational work or include clinical components if appropriate and well-justified.

12) What does "Clinical Trial Optional" mean for applicants?

It means applicants have flexibility in project design: they may submit proposals that are entirely preclinical/translational, or they may propose studies with clinical components if those components are appropriate for the aims and are justified within the application.

13) Is there a specific focus on people with HIV (PWH)?

Yes. The NOFO highlights optimizing vaccine performance for people with HIV (PWH). This reflects that immune status and co-infections can influence vaccine responses and disease risk, and that KSHV-associated conditions are particularly relevant in immunocompromised populations.

14) What kinds of approaches might be considered for optimizing vaccines in PWH?

Projects in this area might examine dosing, adjuvants, schedules, immune correlates, or other strategies intended to maximize vaccine efficacy and durability in people with HIV (PWH), consistent with the NOFO emphasis.

15) Does the NOFO support research on how KSHV is transmitted and how infection begins?

Yes. A stated 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.

16) What kinds of questions about early infection and transmission are in scope?

The NOFO describes understanding how exposure occurs, which tissues or cell types are first infected, and what immune responses are needed at those sites to prevent establishment of infection, all with the aim of identifying actionable vaccine-blockable steps.

17) Why are KSHV detection methods and assay standardization part of the program?

Because consistent, reliable assays are essential for measuring infection, viral load, immune responses, and endpoints needed to evaluate vaccine candidates across studies and eventually in clinical settings. The NOFO calls for optimization and standardization of these methods.

18) What funding mechanism is used for this opportunity?

This opportunity uses a U01 cooperative agreement mechanism.

19) What does a U01 cooperative agreement imply compared with a standard research project grant?

A U01 cooperative agreement typically means NIH program staff will have substantial involvement in coordinating and guiding the overall program compared with a standard research project grant.

20) Which NIH institute is leading this initiative?

The initiative is led by the National Cancer Institute (NCI) within NIH.

21) What are the CFDA listings associated with this opportunity?

The associated CFDA listings are 93.393, 93.395, and 93.399.

22) What are the activity areas for this opportunity?

The activity areas are health and education.

23) What is the original application due date stated in the posting excerpt?

The original application due date listed is December 4, 2024.

24) When was the opportunity created?

The opportunity was created on October 16, 2023.

25) Does the excerpt include an award ceiling or expected number of awards?

No. The excerpt provided does not include an award ceiling or the expected number of awards. Applicants would need to consult the full NOFO for budget and project period expectations.

26) Who is eligible to apply?

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."

27) Are nonprofits eligible even if they do not have 501(c)(3) status?

Yes. The excerpt explicitly lists nonprofits with 501(c)(3) status and nonprofits without 501(c)(3) status as eligible.

28) Are for-profit organizations eligible?

Yes. The excerpt lists for-profit organizations (other than small businesses) as eligible and also lists small businesses as eligible.

29) Are tribal governments and tribal organizations eligible?

Yes. The excerpt includes federally recognized tribal governments and other tribal organizations among eligible applicants.

30) Are institutions of higher education eligible?

Yes. The excerpt includes public and state-controlled institutions of higher education and private institutions of higher education as eligible.

31) Are community-based or faith-based organizations eligible?

The excerpt states that the NOFO explicitly encourages or allows participation by faith-based or community-based organizations.

32) Are historically underrepresented and mission-driven institutions specifically called out?

Yes. The excerpt notes that the NOFO 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, and tribally controlled colleges and universities, among others.

33) Are U.S. territories or possessions included in the eligible/encouraged categories?

Yes. The excerpt includes U.S. territories or possessions among the categories explicitly encouraged or allowed to participate.

34) Are non-U.S. entities (foreign organizations) allowed to participate?

Yes. The excerpt includes non-U.S. entities (foreign organizations) among the categories explicitly encouraged or allowed to participate.

35) What kinds of outcomes is this program aiming to enable?

Based on the excerpt, the program is aiming to enable credible vaccine candidates and the evidence base needed to advance them, including immunogenicity and protection data (often supported by improved animal models), better understanding of transmission and early infection to identify vaccine-blockable steps, and standardized detection/measurement approaches suitable for comparing results across studies and supporting eventual clinical evaluation.