Explore New Solutions in Global Health Priority Areas (Round 16)

The Opportunity

(For additional information, please see the challenge-specific FAQs here)

This call for ideas is part of the 16^th round of Grand Challenges Explorations (GCE). Throughout the preceding 15 rounds, we have experimented with a mix of topics – broad, open topics that leave much to the innovators’ imaginations, and narrow, focused topics that provide a specific toolset or criteria – covering everything from new therapeutics, vaccines, and diagnostics to financial services for the poor and agricultural tools for smallholder farmers. One consistent lesson we have learned is that the world never seems to run out of great ideas. To elicit more of these great ideas without limiting creativity and boldness, we are setting forth a series of challenges that remain broadly unsolved in the areas where we work. Here we provide a bit of guidance around what we will and will not fund, but leave the solution itself open to your imagination.

Above all, our goal is to harness advances in science and technology to save lives, and all of our investments are driven by the need to develop and apply solutions that can be deployed, accepted, and sustained in the developing world.

The challenges laid out below fit squarely within our focus areas and identify gaps in knowledge or technology that, if understood and developed, could launch us forward quickly to save lives and improve the quality of life for the worlds’ poorest.

The Challenge

To encourage innovators around the world to think outside the box and potentially address challenges outside their primary field of work, we are posing a short and concise list of key challenges that remain unmet by the world’s greatest minds. We ask that applicants review our priority funding areas for additional information and consider ideas that can be sufficiently tested within the scope of a GCE Phase I award ($100,000 USD over 18 months). While these are big challenges and we don’t expect complete solutions here, we expect proposals to clearly outline success metrics to help us understand whether the idea will ultimately be transformative. We seek ideas that are "off the beaten track", daring in premise, and clearly different from the approaches currently being developed or employed.

This list is not in order of priority, nor is it an exhaustive list of the challenges we seek to solve; however, for the purposes of this request for proposals, ideas must show clear relevance to one of these specific challenges. More specific information on each challenge and what we will or will not fund can be found after the list.

We’re seeking innovative ideas to assess the burden of disease, to develop better vaccines, and to develop new diagnostics, specifically to:

• Better understand cause of death from tissue samples;
• Develop a quantitative measurement of Mtb bacterial load;
• Develop immunization strategies that increase somatic hypermutation;
• Explore and develop approaches to immunization that drive donor unrestricted cytotoxic T cell responses;
• Develop parenteral vaccines that induce mucosal immunity;
• Develop point-of-care nucleic acid diagnostics to below $2 per test;
• Enable self-testing for cervical cancer;
• Develop malaria diagnostics to accelerate toward eradication.

Successful proposals will:

• Clearly describe how the idea, if successful, would help solve one of the challenges described in the call;
• Be directly relevant to the developing world (e.g. low-cost, useful across multiple geographical and cultural settings, self-sustaining);
• Have a clear and testable hypothesis and include an associated plan for how the idea would be tested or validated;
• Yield interpretable and unambiguous data in Phase I, in order to be considered for Phase II funding.

We are specifically seeking proposals under these categories. Additional information on each can be found below.

Better understand cause of death from tissue samples

In order to get the right interventions to the right children in the right place to save lives, particularly in developing countries, we need to better understand what causes morbidity and mortality. To that end, we are seeking better ways to identify pathogens and immune responses in tissue samples collected at autopsy. We welcome bold ideas to enable identification of pathogens and associated pathology in tissue samples that can overcome one or more challenge including improved reproducibility and robustness of results, faster and simpler tissue processing, and reduced dependence on specific reagents (e.g. available antibodies). Tissue samples of high interest include lung, liver, and brain biopsy samples.  Standard pathology and immunohistochemistry based methods will not be considered for funding.

Develop a quantitative measurement of Mtb bacterial load

Diagnosing active tuberculosis remains a difficult prospect requiring assessment of sputum samples to confirm the presence of bacteria. A simple, cheap, and quantitative test for bacterial load would transform TB diagnosis and treatment, allowing a focusing of time and treatment resources on those with the highest bacterial burden, and therefore greatest likelihood of poor outcomes and high rates of disease transmission. We seek ideas to further our understanding of the total body burden of Mtb including measurement of bacterial populations in the lung that are not present in sputum, bacteria outside the respiratory tract, and bacteria missed using standard culture methods.

Develop immunization strategies that increase somatic hypermutation

To date, most vaccine discovery and development aimed at driving functional B cell responses has not focused on methods for optimizing high affinity antibody responses. Understanding the mechanisms that favor germinal center reactions and the generation of memory B cells able to re-enter germinal centers may provide more effective means for driving high affinity B cell responses with vaccination. We seek proposals to define the mechanisms that can be manipulated in vaccination strategies to drive highly mutated, high affinity (durable) antibodies.

Explore and develop approaches to immunization that drive donor unrestricted cytotoxic T cell responses

For a vaccine to be most effective in an immunization strategy in the developing world, the approach must be broadly applicable, regardless of an individual’s HLA type. To that end, we welcome ideas for new vaccination approaches that drive antigen-specific CD8 T cell functions, such as targeted cell lysis and cytokine production, in a manner which is not MHC class IA restricted. 

Develop parenteral vaccines that induce mucosal immunity

Mucosal surfaces are often either the portal of entry for pathogens or the site where immune responses are coordinated. Depending on the pathogen, mucosal immune responses may contribute to protective immunity or reduced disease transmission. To improve the efficacy of vaccines, we seek to better understand and develop methods by which a peripheral injection generates robust immune responses in the gut. We seek to both better understand the induction and measurement of such responses.

Develop Point-of-care nucleic acid diagnostics to below $2 per test

There is a need for point-of-care tests for nucleic acid targets that are extremely low cost, yet retain the capability of processing diverse sample types (such as sputum, whole blood, stool, swabs, and urine) and the ability to quantitate targets. We seek new diagnostic platforms or technologies that maximize sample preparation flexibility across specimen types, maintain sensitivity and quantitation, and are very low cost, with an end-to-end test cost target of below $2, including sample collection.  Of particular interest are HIV viral load testing, TB case detection, and HPV screening.

Enable self-testing for cervical cancer

We seek methods to allow women to screen themselves for cervical cancer risk, providing a risk determination similar to a Pap smear or HPV DNA test, with high-risk women directed for follow-up assessment and potential pre-cancer treatment or cancer management. The advantage of this format would be increased screening frequency and administration within the privacy of the woman’s home. These methods should be low-cost, easy to use, developed around verified and validated biomarkers detectable with sufficient specificity and sensitivity in the specimen of interest (urine, cervical, or vaginal samples), agnostic to language and culture, be easily used by an adult patient in her home or village, and provide a clear signal to patients who need to seek follow-up assessment.   

Develop malaria diagnostics to accelerate toward eradication

As we drive toward malaria eradication, we seek new ideas for malaria diagnostics to enable the eradication of malaria. Specifically:

• More sensitive diagnostics. In the control phase, microscopy and commercial rapid diagnostic tests (RDTs) seem to be sufficient to carry out the goals of malaria control programs to reduce morbidity and mortality. However, to move from “Control” to “Elimination”, we need more sensitive tests to identify individuals in the community with lower parasite densities who are not diagnosed with current RDTs but contribute significantly to malaria transmission.
• Non-invasive RDTs. As we move toward elimination, we anticipate that it will be difficult to “actively” test the population using finger prick, especially in very low prevalence regions. Therefore, we seek RDTs performed on non-invasive samples such as saliva. To fit the need, these tests must be simple, fully integrated, as sensitive as RDTs performed on blood, and importantly, remain very low cost.

We Will Not Fund:

• Ideas that do not address one of the key challenges described in this call;
• Ideas or solutions not aligned with the Gates Foundation’s Global Health priority areas and strategies listed above;
• Ideas without a clearly-articulated and testable hypothesis;
• Approaches that represent incremental improvements to conventional solutions (e.g., research of current methods for vaccine discovery, development and delivery intended to expand, improve or integrate existing technologies or tools);
• Basic research without clear relevance to the goals of this topic;
• Variations on conventional small molecule and biologic therapeutic approaches (such as those focused on screening for new chemical entities, assays for validation, or tests of drug efficacy) that would yield drug treatment approaches in areas other than malaria or tuberculosis;
• Solely behavioral change/educational initiatives (e.g., training programs, scholarships, education programs);
• Solely infrastructure or capacity-building initiatives;
• Approaches that present unacceptable downstream safety risks (e.g., as a barrier to product development);

For more specific information about the foundation’s strategies in the priority Global Health areas, see: http://www.gatesfoundation.org/What-We-Do