NIAID Wants a Better Malaria Vaccine for $4 Million: RFA-AI-28-024, Five to Seven R61/R33 Awards, One Application Per Institution, Due February 11, 2027

The world has two licensed malaria vaccines, and NIAID's new funding announcement starts by describing their limits. RTS,S/AS01 and R21/Matrix-M "only offer partial, short-term protection in reducing disease in children over five months of age living in endemic areas." Both target one stage of one parasite species's life cycle. Neither blocks transmission well, neither protects adults for long, and neither is intended for Plasmodium vivax, the relapsing species that causes most malaria outside Africa.

RFA-AI-28-024, "Accelerating Research and Development of Next Generation Vaccines against Malaria – a Model for Mosquito-Borne Diseases," posted October 13, 2026. It is NIAID's attempt to fund the next generation of malaria vaccines. The budget is small, $4 million in FY2028 for five to seven awards, and the application rules are restrictive. Groups planning to apply should know three things first: only one application per institution is allowed, foreign subawards are prohibited, and GLP toxicology is excluded even though the preclinical scope reaches IND-enabling work.

Award structure and dates

The opportunity uses the R61/R33 Exploratory/Developmental Phased Award, with clinical trials not allowed:

• R61 phase: up to three years, budgets not expected to exceed $400,000 direct costs per year.
• R33 phase: up to two years, not expected to exceed $750,000 direct costs per year.
• Maximum project period: five years. At the caps, a full award is about $2.7 million in direct costs before indirect costs.
• Funds: NIAID "intends to commit $4M in FY28 to fund 5-7 awards." That figure covers first-year R61 budgets. Awards at the $400,000 direct cap plus a typical university indirect rate cost roughly $600,000 to $700,000 each, so the five-to-seven estimate is consistent with that.
• Application types: New only. Resubmissions are not accepted.
• Dates: the portal opens January 11, 2027. Applications are due February 11, 2027 at 5:00 p.m. local time. Peer review is July 2027, Advisory Council review October 2027, and the earliest start December 2027.

Moving from R61 to R33 is not automatic. Recipients must submit a transition package at least 75 days before the proposed R33 start. It includes an R61 progress report measured against the milestones in the original application. NIH program staff review it, and the R33 benchmarks are negotiated at that point. The milestones you write in February 2027 will be used to decide whether you receive the R33 funding about three years later.

What NIAID will fund

The scope covers both P. falciparum and P. vivax and is divided into discovery and preclinical development.

Discovery and proof of concept includes:

• Novel vaccine concepts using "improved immunogen design or new antigen(s), formulation, novel innovative or modern technology platforms," with "Artificial Intelligence (AI)-guided vaccine design" named as an example.
• Combination concepts: mixing platforms to broaden immune responses, combining multiple protein subunits against one or more biological pathways, and multi-stage vaccines covering the pre-erythrocytic, blood, and sexual stages.
• Vector-targeted concepts: vaccines against "mosquito vector products (e.g., salivary gland proteins) or processes that may help to reduce pathogen infection, transmission or disease."
• Efficacy demonstration in animal models or new approach methodologies (NAMs), defined to include functional assays, in vitro or ex vivo culture systems, and "computational and AI-based approaches." Efficacy means prevention of infection, disease, or, for vivax, relapse.

Preclinical development includes critical assay and process development, formulation improvement, cGMP pilot lot production and release, IND-enabling activities, and regulatory support "required for initiation of Phase I trial."

Three types of applications are non-responsive and will not be reviewed:

1. Concepts "principally focused on Plasmodium parasites other than P. falciparum or P. vivax" (for example P. knowlesi or P. malariae as the main target).
2. Good Laboratory Practice (GLP) toxicology studies in animals.
3. Clinical trial protocol development.

The second item limits how far toward the clinic an award can go. GLP toxicology is usually the largest IND-enabling expense. NIAID will fund a cGMP pilot lot, assay qualification, and regulatory preparation, but not the GLP tox study. An R33 that plans to finish with an IND filing therefore needs a funding source for that study. NIAID's preclinical services contracts and a partner organization are the usual candidates, and the plan should say which.

Why "a model for mosquito-borne diseases" is in the title

The title and purpose statement present malaria as a model. NIAID describes the goal as protection that can "save lives, strengthen public health security in the United States, and serve as a model for, or are potentially effective against, other mosquito-borne diseases."

This is a deliberate choice. In 2023 the United States had its first locally acquired malaria cases in two decades, in Florida, Texas, Maryland, and Arkansas, and the NOFO's background notes malaria "poses a significant risk for U.S. citizens abroad." Framing the work in terms of domestic health security and multiple vector-borne pathogens makes the case for funding it as more than a global health program.

Applicants should use the same framing where it is accurate. Vector-salivary-protein work applies most directly: an immune response to Anopheles or Aedes saliva could affect transmission of more than one pathogen, and the NOFO lists that work as in scope. Platform and immunogen-design work (structure-guided antigen design, AI-assisted epitope selection, new adjuvant formulations) can describe its relevance to dengue, Zika, chikungunya, or West Nile without overstating it. The criterion is that the work could serve as a model or could be effective against other diseases. Your Significance section should address it directly.

The rules that will cause trouble

One application per institution. This limit is unusual for an R61/R33, and it applies by UEI or NIH IPF number. A university with malaria groups in several departments (immunology, a vaccine center, a structural biology institute) can submit only one. Ask your research office now whether it will run an internal limited-submission review. If it will, its internal deadline is effectively your deadline, and it is probably in November or December. Companies, including small businesses, are eligible and also limited to one application each, which helps biotechs with a single platform.

No foreign subawards. Foreign organizations may apply directly, and foreign components are allowed. But under NIH's current policy, "applications involving foreign subawards/subcontracts submitted in response to this NOFO will be deemed noncompliant." For malaria research this matters a great deal: much of the field depends on partnerships with endemic-country sites for parasite isolates, field sera, and controlled infection models. Under this NOFO you can work with those partners as unfunded collaborators, pay foreign consultants, and buy unique reagents from foreign vendors, but you cannot send them a subaward. Plan the budget accordingly, and see our explainer on NIH's foreign-subaward restrictions and the collaborative international award path. An endemic-country institution with its own strong program can also apply as the prime applicant.

Required Product Development Plan. Applicants must upload a separate "Product Development Plan.pdf," up to four pages. It cannot be used to extend the 12-page Research Strategy. Reviewers will judge it as an indicator of whether the team understands the path to a product. It should cover a draft target product profile, the regulatory pathway, manufacturability, and how the GLP tox gap will be filled.

Writing milestones that work for go/no-go decisions

The review criteria specific to this NOFO concern decision-making. Reviewers will evaluate "the clarity and appropriateness of the criteria to support translational Go/No-go decisions in selection of vaccine candidates," and whether the R61 transition milestones are "adequately described, quantifiable, and achievable." The NOFO asks for SMART milestones and suggests a Gantt chart.

In practice, every R61 milestone should be a quantitative threshold with a decision attached. For example: sterile protection in a stated percentage of animals at a stated challenge dose, functional antibody titers above a named comparator in a standard membrane feeding assay, or durability of response at a specified number of weeks. Each should say what you will do if the threshold is missed: drop the candidate, reformulate, or return to design. Milestones such as "characterize the immune response" give reviewers nothing to evaluate and give program staff nothing to approve at transition. The R33 plan may be "broad and somewhat speculative" because it depends on R61 results, but the criteria for entering the R33 must be specific.

Benchmarking against the existing vaccines is also useful. If your candidate is intended to beat RTS,S or R21 on durability, transmission blocking, or vivax coverage, state the margin and how you will measure it in the R61. The NOFO's background defines the target as better than partial, short-term protection.

Who should apply

The best-positioned applicants are groups with a lead candidate and preliminary data who want two to five years of support moving from concept toward the cGMP and regulatory work needed for Phase I. Structural vaccinology labs with new antigen designs, adjuvant and formulation groups, and companies with platforms that have shown promise in other pathogens fit well. Groups studying basic immunology without a candidate are a weaker fit. A phased award judged on go/no-go criteria rewards applicants who have a product in development.

If you are working on a different part of NIAID's portfolio, our coverage of the NIAID ReVAMPP pandemic preparedness network shows how the institute is organizing prototype-pathogen work across viral families.

With one application per institution and a February 11 deadline, the internal selection may decide your chances more than federal review will. Granted can help you draft milestones, the product development plan, and the significance argument in time for your institution's limited-submission review.