Awarded Grants

Marion Jourdan of Danone Nutricia Research in the Netherlands together with Michael Zimmermann of ETH Zürich in Switzerland will test an approach to enhance iron absorption from food in children in Kenya by providing them with live food-grade bacteria to release phytate-bound iron from popular foods such as cereal flour. Phytates bind strongly to iron and inhibit its absorption. Their previous work identified different bacterial strains containing phytases that could grow in milk, degrade phytates, and release nutritionally-relevant levels of free iron in vitro. They will test different strain combinations for their phytate-degrading activity under different conditions, such as in specific foods and in an environment mimicking the upper GI tract, and select the best one for producing a fermented food product. This will then be tested to assess its effect on iron absorption in a cohort of 22 iron-deficient Kenyan school-aged children.

Jurriaan de Steenwinkel of the Erasmus Medical Center Rotterdam in the Netherlands together with Eric Nuermberger of Johns Hopkins University in the U.S. will combine expertise to develop a robust, preclinical mouse model of latent tuberculosis (TB) together with a molecular assay for measuring candidate drug activity to boost drug development. Reducing latent TB infections is essential to meet the goal of the World Health Organization’s End TB Strategy but current drugs have limited effect and measuring the activity of candidate compounds in latent infections is challenging. Successfully developing new drugs also requires improved preclinical models that identify drug candidates more likely to be effective in the clinic. They will combine their paucibacillary murine TB model with their first-in-class RS ratio assay, which quantifies rRNA synthesis in the causative Mycobacterium tuberculosis, and test its value for identifying new drugs that can more rapidly and effectively cure patients also with latent infections.

Rakhi Dandona of the Public Health Foundation of India will examine gender disparities in national health programs in India by harnessing existing large-scale gender-specific data for disease burden and their risk factors from the Global Burden of Disease Study to help address gender-based health inequities in India. Males and females are affected differently by many diseases. The researchers will examine three national health programs in India covering various age-groups, specifically adolescent health, the elderly, and mental health, for gender-specific disease and risk estimates to assess where more focus is needed on girls and women. This would facilitate gender-specific health interventions within the existing national health programs and identify potential new programs to achieve better health outcomes for women and girls.

Munyaradzi Musvosvi of the University of Cape Town in South Africa will determine whether a valuable biomarker of tuberculosis (TB) can be measured in small volumes of blood collected by finger-prick together with an automated, low-cost processing approach to accelerate diagnoses in low-resource settings. Individuals with TB have higher levels of a specific activation marker on the surface of some of their T cells, which could be a valuable diagnostic target. However, current methods to measure levels requires trained health and laboratory professionals to draw the blood, perform the assay, and analyze the results. As a more practical approach for resource-limited settings, they will test whether the biomarker can be reliably measured in low volumes of blood. They will also develop a microfluidic device to automatically process blood samples for flow cytometry analysis, and novel staining reagents as an alternative to expensive antibodies.

Rachel Chikwamba of the Council for Scientific and Industrial Research in South Africa together with Kerry Love of Sunflower Therapeutics in the U.S. will establish local manufacturing capacity in South Africa to increase access to protein-based biologic drugs including antibodies and vaccines, which are used for treating many different diseases. Access to biologics is unevenly distributed across the globe, and the conventional manufacturing practices are expensive and require substantial physical space and operational know-how. They have established low-cost, automated and modular manufacturing systems that can be easily adapted to different biologics and changing market needs. They will determine current local and regional needs and capabilities associated with biologics, identify five initial products for development, and produce business models for commercialization that can be used as a roadmap for the successful local deployment of their biologics manufacturing technology.

Sana Syed of the University of Virginia in the U.S. together with Imran Nisar of Aga Khan University in Pakistan will utilize metabolic modeling of patient-derived ‘omics data from pre-existing maternal and pediatric cohorts to identify new biomarkers and therapeutic targets for environmental enteropathy (EE), which is associated with impaired childhood growth and development and vaccine responses. They will leverage a computational, flux-balance analysis-based approach to analyze large transcriptomic and proteomic datasets from pregnant mothers and infants with EE to identify disease-associated metabolic signatures. The signatures derived from pregnant mothers might precede the development of EE and reveal pharmaceutical targets for prevention. They will also develop a duodenal enteroid cell culture model derived from biopsies of children with EE to test whether the identified infant-derived metabolic signatures can be disrupted with existing pharmacological agents as potential new treatments.

Adriana Bonomo of Fiocruz in Brazil together with Penny Moore of the National Institute for Communicable Diseases in South Africa will identify solutions for combating new SARS-CoV-2 variants by developing an in vitro assay to predict new variants and identifying broad specificity antibodies for use as new drugs and diagnostics. Despite the success of vaccines and antibody therapies, the continual emergence of new viral variants, which thwart our immune defenses and therapies, remains a major challenge of the pandemic. They will develop a virus training assay by culturing existing variants with hyper-immune sera from infected individuals in South Africa and Brazil to drive selection of new mutations and identify potential new variants. They will also isolate new monoclonal antibodies directed to conserved cleavage sites of the viral spike protein, which are essential for it to infect cells, that could be used as treatments to block infection by a wide range of variants.

Seth Bloom of Massachusetts General Hospital in the U.S. together with Sinaye Ngcapu of the Center for the AIDS Programme of Research (CAPRISA) in South Africa will investigate how bacterial vaginosis (BV) and non-Lactobacillus-dominated vaginal microbiota elevate the risk of contracting HIV-1 to help develop preventative therapies. South Africa has high rates of BV and microbiota-associated vaginal HIV transmission but the underlying mechanisms are unknown, which makes it difficult to prevent. The researchers will combine samples from South African cohorts with innovative in vitro assays to test their hypothesis that bacterially-produced putrescine, which is a BV-associated metabolite, in the cervicovaginal mucosa enhances HIV risk by increasing the post-translational modification and thereby activation of a molecule involved in promoting HIV protein production. They will also test existing inhibitors of this pathway as novel, pre-clinical HIV prevention candidates to establish the groundwork for a clinical trial.

Penny Moore of the National Institute for Communicable Diseases in South Africa together with Adriana Bonomo of Fiocruz in Brazil will identify solutions for combating new SARS-CoV-2 variants by developing an in vitro assay to predict new variants and identifying broad specificity antibodies for use as new drugs and diagnostics. Despite the success of vaccines and antibody therapies, the continual emergence of new viral variants, which thwart our immune defenses and therapies, remains a major challenge of the pandemic. They will develop a virus training assay by culturing existing variants with hyper-immune sera from infected individuals in South Africa and Brazil to drive selection of new mutations and identify potential new variants. They will also isolate new monoclonal antibodies directed to conserved cleavage sites of the viral spike protein, which are essential for it to infect cells, that could be used as treatments to block infection by a wide range of variants.

Peter van Heusden of the University of the Western Cape in South Africa together with Placide Mbala of the Institut National de Récherche Biomedicale in the DRC will establish in-house pathogen sequencing capabilities at a research institute in the DRC to enable rapid responses to meningitis outbreaks and improve patient outcomes. Despite the success of vaccines, meningitis outbreaks caused by diverse bacterial species still cause substantial fatalities across Africa. Diagnosis of the latest outbreak in the DRC was delayed for several months because samples had to be transported out of the country for genomic sequencing. They will leverage a field-portable sequencer with bioinformatics processor to build a platform with a user-friendly interface for use in a low-infrastructure setting. They will also train local scientists to extract DNA from patient samples, run the sequencer, and interpret the results so that they can provide rapid surveillance of meningitis-causing pathogens directly in the DRC.