Awards

James Beeson of Burnet Institute in Australia, Melissa Kapulu of Health Research Operations Kenya Limited in Kenya, Isaac Ssewanyana of Infectious Diseases Research Collaboration in Uganda, Faith Osier of Imperial College London in the U.K. and Pras Jagannathan of Stanford University in the U.S., will analyze clinical samples using an antibody functional assay platform with malaria antigen arrays to identify antigens targeted by protective antibodies for next-generation malaria vaccines. They will identify antigen-specific functional antibodies that strongly correlate with protective immunity to malaria observed in clinical studies with two populations: Kenyan adults after controlled experimental challenge infection with Plasmodium falciparum and children followed longitudinally who were naturally exposed in Uganda and in Papua New Guinea. They will then use biostatistical modeling approaches to identify antigen and functional antibody types that most frequently occur in protective combinations, identifying additive and synergistic combinations of responses and responses most predictive of protective immunity across age groups and populations. This will enable prioritization of antigens and their combinations for malaria vaccine candidates.

Rajshekhar Karpoormath of the University of KwaZulu-Natal in South Africa will test a set of potential anti-TB hit compounds against clinically relevant TB strains, using the results to generate optimized hit compounds for development of new anti-TB drugs. They will screen the potential hits against susceptible, monodrug-resistant, multidrug-resistant, and extensively drug-resistant TB strains as well as other Mycobacterium strains. The screening results will inform structure-based drug design to generate optimized hit compounds. Potential lead hits will be screened again, with the most promising evaluated against intracellular bacteria in macrophages, tested for in vitro cytotoxicity, and evaluated for mechanism of action in bioassays including carbon-isotope tracing metabolomics and an in vitro granuloma assay.

Moses Obimbo Madadi of the University of Nairobi in Kenya and Aida Sivro of the University of Manitoba in Canada will determine the molecular epidemiology of human papillomavirus (HPV) in cervical cancer cases in Kenya to enable monitoring of changes in the prevalence of HPV types targeted by current vaccines and detect possible replacement with other types. They will perform a cross-sectional study on Kenyan women being followed-up for cervical cell abnormalities at hospitals in Nairobi and in rural Kenya. Outcome measures will include prevalence of HPV genotypes by age, geographic location, and HIV status. HPV genotypes will be stratified by cervical diagnosis to determine the top genotypes associated with cervical cancer. This research will provide robust and standardized statistics on the burden and genetics of oncogenic HPV infection in Kenyan women.

Wambui Nyabero of Medevice Kenya in Kenya and Vibhav Joshi of InnAccel Technologies Pvt Ltd in India will pilot test Fetal Lite, a fetal monitor for early detection of fetal distress to reduce intrapartum mortality. The monitor is designed for ease of use and patient comfort. It measures fetal and maternal heart rate and uterine activity, has automated data analysis with audio and visual alerts, and has a built-in electronic partogram and AI-based pregnancy risk scoring. It is cloud-enabled with a central web dashboard for report sharing and trend monitoring. They will deploy devices in medical facilities associated with the University of Nairobi, measuring the quality of the auto-generated analysis compared to blinded expert annotation and the ease of use by nursing staff. They will also capture the associated birth outcomes, the guidance provided through remote monitoring, and the number of detected fetal distress cases and referrals.

Daniel Muema of the KAVI Institute of Clinical Research, University of Nairobi in Kenya and Marit J. van Gils of the University of Amsterdam in the Netherlands will characterize the B cell immune repertoire in defined African populations to inform the use of an HIV vaccine with a germline-targeted immunogen. This clinically advanced, HIV envelope glycoprotein immunogen, BG505 SOSIP GT1.1, is engineered to guide the development of naïve B cells to produce broadly neutralizing antibodies (bnAbs) against HIV. They will determine the baseline frequencies of bnAb-precursor naïve B cells and bnAb-like memory B cells that recognize this immunogen in uninfected, adult sex workers highly exposed to HIV and in adults living with HIV. This will determine if the immunogen will be effective in these populations for HIV prophylaxis and functional cure, informing the design of vaccine clinical trials.

Seth Bloom of Massachusetts General Hospital and Margaret Kasaro of the University of North Carolina Global Projects Zambia in Zambia will validate metabolite biomarkers of clinically-relevant, vaginal microbiota community state types (CSTs) for development of diagnostics for research and clinical care. Different CSTs confer distinct risks for diseases linked to bacterial vaginosis, including risk of preterm birth and HIV infection. They will validate in a Zambian cohort the CST metabolite biomarkers that they previously identified in a South African cohort. They will grow pure cultures of individual bacteria to identify species and candidate enzymes responsible for vaginal CST biomarker production or consumption to inform development of a diagnostic assay. An inexpensive, real-time, point-of-care, diagnostic assay for use in low-resource settings would remove the need for slower, costlier DNA sequencing methods. Such a diagnostic test for vaginal microbiota-associated diseases will improve diagnosis, prediction of clinical risk, and monitoring of responses to therapy.

Digby Warner of the University of Cape Town in South Africa and Catherine Blish of Stanford University in the U.S. will explore human precision-cut lung slices (hPCLS) as an Mtb bioaerosol detection platform and model system for infection. Such a platform would provide an immediate read-out of Mtb infectivity and give insights into the initial Mtb-host interaction. They will determine the feasibility and reproducibility of using the hPCLS platform with samples containing extremely low numbers of Mtb bacilli, monitoring bacterial infectivity, replication, and dissemination by time-lapse fluorescence microscopy and examining key early events by cytometric and single-cell molecular assays. The platform could be used to answer specific questions, including whether Mtb organisms released during coughing by symptomatic TB patients are more infectious than those aerosolized during normal respiratory activities by asymptomatic individuals. It could also be applied at the site of aerosol sampling to guide and monitor preventative and therapeutic interventions.

Leon Tshilolo of the Institut de Recherche Biomédicale 1-Health in the Democratic Republic of Congo and Johnny Mahlangu of University of the Witwatersrand in South Africa will perform a pilot study using a mobile laboratory to conduct sickle cell disease (SCD) screening and patient follow-up in hard-to-reach and rural areas of the DRC. A mobile laboratory could lead to broader and earlier detection of SCD, enabling treatment sooner, and help ensure continued treatment, together reducing mortality and improving health outcomes. Sickle cell carriers will also be identified, with the study contributing to a more accurate epidemiological map of SCD to guide national healthcare strategy and advocacy efforts.

Erica Andersen-Nissen of Hutchinson Center Research Institute of South Africa and Gerhard Walzl of Stellenbosch University, both in South Africa, will perform bronchoalveolar lavage in volunteers receiving the BCG or MTBVAC vaccine intradermally in the HVTN 605 clinical trial to delineate vaccine-induced lung immune responses and identify correlates of protection. Lavage will be performed pre- and post-vaccination, and cells isolated from the lavage fluid will be analyzed for protein expression and by transcriptional profiling. They will compare the lung immune response they detect with the blood immune response identified in the large datasets available as part of the trial. Correlations between them could identify human blood biomarkers of lung T-cell responses that protect against TB. Such biomarkers will inform ongoing and future studies of immune correlates of efficacious TB vaccines.

Rajeev Shrestha of Dhulikhel Hospital Kathmandu University Hospital in Nepal with the Institute of Tropical Medicine Antwerp in Brussels and Paul Pronyk of National University of Singapore in Singapore will establish an integrated surveillance platform to speed the detection of dengue and the response to dengue outbreaks in Nepal. The platform will encompass dengue surveillance at multiple levels. Ecological and community-based surveillance will incorporate population-based, longitudinal dengue serosurveys to identify dengue hotspots. Hotspot mapping will integrate meteorological data for targeted mosquito vector surveillance, including serotype-specific detection of dengue virus in mosquitoes. Hospital-based surveillance will combine PCR-based dengue detection with information on clinical outcomes at sites across diverse geographical locations in Nepal, and genomic profiling will be performed for a subset of these circulating dengue strains. The integrated platform will serve national health authorities and policymakers, while setting the stage for similar platforms targeting additional emerging infectious diseases.

Jo-Ann Passmore of the University of Cape Town in South Africa and Elizabeth Bukusi of KEMRI in Kenya will determine the effects of the antibiotic metronidazole on bacterial vaginosis (BV)-associated microbes to guide the development of a live biotherapeutic product (LBP). BV is treated with antibiotics like metronidazole (MTZ), but recurrence is high, and an LBP could sustainably interrupt BV. They will compare temporal changes in abundance of BV-associated bacteria in women from Kenya and South Africa receiving MTZ treatment, and they will evaluate the impact of MTZ treatment on cervicovaginal inflammatory profiles. They will also compare antibiotic resistance prevalence and profiles for BV-associated bacterial strains isolated from these women, before and after MTZ treatment. The results will guide the interpretation of ongoing and future LBP efficacy studies, as well as generating a panel of BV-associated bacterial strains that can be screened to help select new candidate LBP strains.

George Wamukoya of African Group of Negotiators Experts Support (AGNES) in Kenya and Seyram Agbemenya of Africa Capacity Building Foundation in Ghana will establish an African hub of technical support for country teams to develop proposals for climate change adaptation projects fundable by the public and private sectors and philanthropies. They will pilot the approach through proposal writing workshops bringing together teams across at least three countries. The teams will include experts from the government, private sector, and academia. Together, they will profile the risks as described in the climate policy documents for their respective countries to build a business case, while analyzing the international climate finance landscape to identify aligned funding opportunities. They will take a portfolio approach to identify a strategic pipeline of projects to accelerate climate change adaption in Africa.

Jacqueline Weyer of the National Institute for Communicable Diseases in South Africa and Jinal Bhiman of Wits Health Consortium (Pty) Ltd also in South Africa will leverage a rapid monoclonal antibody (mAb) isolation and screening pipeline to develop diagnostics that differentiate between pathogens to support epidemic responses. Africa’s burden of many zoonoses and vector-borne diseases (VBD), such as Lassa fever and yellow fever, remains largely unknown, mainly due to diagnostic costs and limited access to reagents. They will leverage an existing screening pipeline, with infrastructure established by the Global Immunology and Immune Sequencing for Epidemic Response - South Africa (GIISER-SA) project, using a mouse model as a more readily available source of pathogen-specific B cells to identify mAbs that detect three ebolavirus species. These mAbs will be tested for sensitivity and specificity using patient samples and can be used to develop immunoassays, including rapid lateral flow assays, which are important for rapid, field-based diagnosis.

Anne Lee of Brigham and Women's Hospital in the U.S. and Yasir Shafiq of Aga Khan University in Pakistan will develop geospatial models to predict risks of undernutrition among adolescent girls and pregnant and lactating women in settings affected by conflict, climate and COVID-19 to help target interventions. Globally, around 30–40 million pregnant women and 50 million adolescent girls are underweight. Risks of undernutrition have recently been amplified by numerous armed conflicts, climatic shocks such as flooding and the COVID-19 pandemic. However, real-time data shortages prevent interventions, such as balanced energy-protein supplements, from reaching the highest-risk groups. Using Bayesian Hierarchical Spatial modeling, they will develop geospatial models for countries vulnerable to conflict and climate change, such as Ethiopia and Yemen. By incorporating socio-demographic and economic indicators, and climate-related and conflict-related shocks from national databases, they can estimate risks based on exposure and predict outcomes, such as undernutrition and anemia.

Margaret Kasaro and Soumya Benhabbour of the University of North Carolina at Chapel Hill in the U.S. will evaluate 3D-printed intravaginal ring (IVR) prototypes in Zambia to identify the design most acceptable to women for long-term use against unplanned pregnancy and HIV infection. In Zambia, HIV prevalence remains particularly high among women, and 41% of pregnancies are unplanned. IVRs are an effective, well-tolerated, and women-controlled contraceptive and HIV-preventative; however, their performance has suffered in large-scale clinical trials because of poor adherence. They have exploited a state-of-the-art 3D-printing process to rapidly engineer IVRs in a cost-effective, single-step process enabling the controlled release of multiple drugs for HIV prevention and contraception. They will recruit around 16 women, aged 18–45 from Kampala Health Centre, and use focus groups to evaluate their views on the proposed 90-day timeframe of use for four different IVR prototypes to guide the final design.

Yasir Shafiq of Aga Khan University in Pakistan and Anne Lee of Brigham and Women's Hospital in the U.S. will develop geospatial models to predict risks of undernutrition among adolescent girls and pregnant and lactating women in settings affected by conflict, climate and COVID-19 to help target interventions. Globally, around 30–40 million pregnant women and 50 million adolescent girls are underweight. Risks of undernutrition have recently been amplified by numerous armed conflicts, climatic shocks such as flooding and the COVID-19 pandemic. However, real-time data shortages prevent interventions, such as balanced energy-protein supplements, from reaching the highest-risk groups. Using Bayesian Hierarchical Spatial modeling, they will develop geospatial models for countries vulnerable to conflict and climate change, such as Ethiopia and Yemen. By incorporating socio-demographic and economic indicators, and climate-related and conflict-related shocks from national databases, they can estimate risks based on exposure and predict outcomes, such as undernutrition and anemia.

Raghavan Varadarajan in collaboration with Sudha Kumari, both of the Indian Institute of Science in India and Nico Callewaert of the VIB-UGent Center for Medical Biotechnology in Belgium will modify the microorganism, Pichia pastoris, used to produce lower-cost vaccines in low-resource settings, to generate more effective vaccines. Many vaccines are composed of pathogen-derived proteins that require production inside other cells. Although P. pastoris can produce these antigens at a lower cost than mammalian or insect cells, the viral proteins it produced for the SARS-CoV-2 vaccine were hyperglycosylated and poorly immunogenic, unlike those produced in mammalian cells. They will express different antigen forms in mammalian cells, and in different Pichia hosts, to determine whether altering glycosylation and protein size affects immunogenicity. They will also glycoengineer Pichia hosts to determine whether they can produce more effective vaccines. Ultimately, this approach could improve vaccine production for COVID-19 and other viruses.

Jinal Bhiman of Wits Health Consortium (Pty) Limited in South Africa and Jacqueline Weyer of the National Institute for Communicable Diseases also in South Africa will leverage a rapid monoclonal antibody (mAb) isolation and screening pipeline to develop diagnostics that differentiate between pathogens to support epidemic responses. Africa's burden of many zoonoses and vector-borne diseases (VBD), such as Lassa fever and yellow fever, remains largely unknown, mainly due to diagnostic costs and limited access to reagents. They will leverage an existing screening pipeline, with infrastructure established by the Global Immunology and Immune Sequencing for Epidemic Response - South Africa (GIISER-SA) project, using a mouse model as a more readily available source of pathogen-specific B cells to identify mAbs that detect three ebolavirus species. These mAbs will be tested for sensitivity and specificity using patient samples and can be used to develop immunoassays, including rapid lateral flow assays, which are important for rapid, field-based diagnosis.

Simon Kariuki of the Liverpool School of Tropical Medicine, Kenya in Kenya and Holden Maecker of Stanford University in the U.S. will determine whether probiotics and synbiotics can boost infant immune responses to vaccines. Diarrhea is the second leading cause of death in young children, with rotavirus a leading culprit. Oral rotavirus vaccines are routinely administered in low- and middle-income countries (LMIC) but are only 50% effective compared to 85–98% effectivity in high-income countries. One major cause could be environmental enteric dysfunction (EED), which is pervasive in children in LMIC. Their clinical trial of 600 newborns from western Kenya indicated that administering weekly probiotics and synbiotics (Lactobacilli and Bifidobacteria) up to age six months improved gut health and prevented EED-associated inflammation. They will use stored plasma samples and vaccination records to determine the impact of EED and systemic inflammation, as well as pro- and synbiotic effects on rotavirus vaccine efficacy.

Georgia Tomaras and Nathanial Chapman of Duke University and Girija Goyal and Don Ingber of the Wyss Institute at Harvard University, both in the U.S., will test whether Organ-on-a-Chip technology can inform how antibodies protect humans from pathogen infections to design more effective vaccines. Identifying protective vaccine features and validating them in human clinical trials is time-consuming and costly. An alternative is to use primary human organ chips that reproduce human physiology in vitro. They will stimulate peripheral blood mononuclear cells on the human lymph-node-on-a-chip with existing COVID vaccines and extensively characterize the resultant antibodies, including evaluating epitope specificity, and isotype and glycan profiling. They will also assess the capacity of these antibodies to prevent or reduce SARS-CoV-2 infection using the lung-on-a-chip technology. This approach can ultimately be applied to other pathogens, such as those causing malaria.

Cameron Myhrvold of Princeton University and Mireille Kamariza of the University of California, Los Angeles, both in the U.S., will develop an assay to rapidly detect multiple drug resistance mutations in Plasmodium falciparum and Mycobacterium tuberculosis for malaria and tuberculosis (TB) surveillance, respectively. Malaria and TB are two of the world's deadliest infectious diseases. Rapid and accurate drug resistance testing can save lives but current assays are slow or difficult to scale. Combinatorial Arrayed Reactions for Multiplexed Evaluation of Nucleic acids (CARMEN) is a CRISPR-based diagnostic test that detects nucleic acid biomarkers, such as those in pathogens, with high specificity and throughput. They have developed microfluidic CARMEN (mCARMEN), which produces results in under five hours, and will use an algorithm to design assays that detect the top ten drug-resistant P. falciparum mutations from blood samples, and M. tuberculosis mutations from saliva samples that confer resistance to two first-line TB drugs.

Maurício Barreto and colleagues of Fiocruz in Brazil, together with Alexa Heeks and colleagues of the Health Foundation of South Africa in South Africa, will employ real-world data from two large countries of the Global South to develop a common data model of infectious diseases affecting pregnant women to identify causes and aid intervention development. Centro de Integração de Dados e Conhecimentos para Saúde (CIDACS), together with the Western Cape Provincial Health Data Centre (WCPHDC), have built data systems to utilize routinely collected health data for exploring disease impacts. They will leverage these data systems to explore the impact of gestational syphilis in Bahia, Brazil, and tuberculosis in the Western Cape province of South Africa, and the coverage and effects of screening interventions. Teams will include data curators, analysts and scientists, who will perform data discovery and processing, alongside epidemiologists, clinicians and public health specialists, who will perform epidemiological analyses and community engagements.

Alexa Heeks and colleagues of the Health Foundation of South Africa in South Africa, together with Maurício Barreto and colleagues of Fiocruz in Brazil, will employ real-world data from two large countries of the Global South to develop a common data model of infectious diseases affecting pregnant women to identify causes and aid intervention development. Centro de Integração de Dados e Conhecimentos para Saúde (CIDACS), together with the Western Cape Provincial Health Data Centre (WCPHDC), have built data systems to utilize routinely collected health data for exploring disease impacts. They will leverage these data systems to explore the impact of gestational syphilis in Bahia, Brazil, and tuberculosis in the Western Cape province of South Africa, and the coverage and effects of screening interventions. Teams will include data curators, analysts and scientists, who will perform data discovery and processing, alongside epidemiologists, clinicians and public health specialists, who will perform epidemiological analyses and community engagements.

Seth Adu-Afarwuah of the University of Ghana in Ghana and Julie Croff of Oklahoma State University Center for Health Sciences in the U.S. will assess the effects of nutritional supplementation on adolescent brain development in low-resource settings to support interventions. Nutritional behavior majorly impacts the rapid stage of adolescent neurodevelopment, which in turn impacts future generations through effects on maternal and paternal nutritional status, cognition and parenting. However, little is known about typical adolescent neurodevelopment in low- and middle-income countries, where 90% of the world’s adolescents live. They will recruit 40–60 post-pubertal adolescents in Accra, Ghana, measure their corticolimbic system development over nine months, and assess their problem-solving, planning and cognitive functioning. In another cohort of 40–60 post-pubertal adolescents, they will measure adherence to an eight-month twice-daily micronutrient supplementation program and associated nutritional outcomes.

Julie Croff of Oklahoma State University Center for Health Sciences in the U.S. and Seth Adu-Afarwuah of the University of Ghana in Ghana will assess the effects of nutritional supplementation on adolescent brain development in low-resource settings to support interventions. Nutritional behavior majorly impacts the rapid stage of adolescent neurodevelopment, which in turn impacts future generations through effects on maternal and paternal nutritional status, cognition and parenting. However, little is known about typical adolescent neurodevelopment in low- and middle-income countries, where 90% of the world’s adolescents live. They will recruit 40–60 post-pubertal adolescents in Accra, Ghana, measure their corticolimbic system development over nine months, and assess their problem-solving, planning and cognitive functioning. In another cohort of 40–60 post-pubertal adolescents, they will measure adherence to an eight-month twice-daily micronutrient supplementation program and associated nutritional outcomes.

Brigida Rusconi of Washington University in the U.S. will determine whether female infants develop long-lived antibodies against gut bacteria that subsequently both protect against bacterial infections and promote healthy gut immune and microbiota development in their offspring. Enteric bacterial infections are leading causes of infant morbidity in low- and middle-income countries. Using their mouse model, they found that mothers lacking IgG antibodies, which normally develop before weaning, are unable to provide passive protection against enteric infections to their pups. They will adapt their microbial flow cytometry to test whether maternal serum IgGs react more strongly to infant gut bacteria, suggesting establishment in infancy, and whether they provide passive immunity during pregnancy. They will also analyze plasma from two-year-old infants to identify those with weak IgG reactivity and potential causes. Finally, using a malnutrition cohort in Pakistan, they will train local bioinformaticians and assess whether malnutrition inhibits anti-gut commensal IgG responses.

Daniel Kiboi of the Jomo Kenyatta University of Agriculture and Technology in Kenya will assess whether a novel mutation in the human malaria parasite, Plasmodium falciparum, can be used as a marker to identify drug-resistant malaria and protect key antimalarial drugs. Emerging P. falciparum variants resistant to the three frontline drugs kill millions of people annually but are hard to detect. A better understanding of how these variants resist the actions of existing drugs can help to develop more effective drugs. They previously used a mouse malaria model to produce Plasmodium parasites resistant to all three main drugs and identified the candidate mutated protein likely causing this resistance. They will use in silico bioinformatics analysis, CRISPR/Cas9 approaches, and in vitro drug susceptibility assays to evaluate and validate this mutant protein and determine its role in drug resistance in the human malaria parasite.

Yingda Xie of Rutgers New Jersey Medical School in the U.S. and Joaniter Nankabirwa of Makerere University in Uganda will use CRISPR-based technology to monitor respiratory, food-borne and antimicrobial-resistant pathogens in Ugandan wastewater. A recent Ebola outbreak in Uganda highlights the need for routine multi-pathogen surveillance. However, the vast quantities and diversities of microbes in wastewater make it hard to identify those that might cause deadly outbreaks. They will combine CRISPR-based diagnostics with the recently developed multiplex assay, Combinatorial Arrayed Reactions for Multiplexed Evaluation of Nucleic acids (CARMEN), which enables highly sensitive and specific detection of over 150 nucleic acid sequences from dozens of samples in parallel. They will assess the performance of a field-deployable CRISPR assay to monitor specific pathogens in hospital sewage lines of Mulago Hospital. They will also leverage CARMEN to broadly survey for high-priority outbreak pathogens, including Ebola and yellow fever, in Kampala’s regional wastewater sources.

Carl Lachat of Ghent University in Belgium and Firehiwot Workneh of Addis Continental Institute of Public Health in Ethiopia will assess nutrient gaps in adolescent girls and the feasibility of providing supplements to break intergenerational cycles of poor growth and development in Burkina Faso and Ethiopia. Annually, around 21 million adolescent girls in low- and middle-income countries become mothers, with their infants at increased risk of impaired development. This may be caused by nutrient competition as both pregnancy and adolescence are nutrient-demanding phases. Supplementation with balanced energy-protein (BEP) during pregnancy increases birth weight with sustained benefits during infancy, but how this intervention could be tailored to adolescent girls is unclear. They will use a probability of adequacy approach to evaluate the diets and nutrition of 200 adolescent girls. They will also assess adolescent girls’ acceptability of paying for and taking BEP supplements in rural settings using group discussions and questionnaires.

Herman Pontzer of Duke University in the U.S. and Patricia Ukegbu of the Michael Okpara University of Agriculture in Nigeria will track the daily energy expenditures and requirements, and nutritional statuses of adolescent girls in rural Nigeria to help support their growth and development. Low- and middle-income countries suffer greatly from undernutrition, poor dietary practices and food insecurities, but are also experiencing increased obesity and unhealthy weight gain. Adolescents are particularly vulnerable to poor nutritional health but often neglected in nutritional program planning due to a lack of accurate data. To address this, they will recruit fifty female adolescents aged 13–18 from selected urban and rural schools in Abia State and measure their daily energy expenditure (kcal/d) and body composition (fat%) using the gold-standard doubly-labeled water method. This will be combined with dietary, food security and physical activity assessments to develop an accurate evaluation of nutritional health.

Kathryn Holt of the London School of Hygiene and Tropical Medicine in the United Kingdom and Senjuti Saha of the Child Health Research Foundation (CHRF) in Bangladesh, along with FTIR experts Luísa Peixe and Angela Novais from the University of Porto, will establish Fourier-Transform infrared (FTIR) spectroscopy in a pediatric microbiological diagnostics laboratory in Bangladesh to support clinical and infection control decisions. FTIR is a relatively low-cost, reagent-free technique that can discern different pathogen strains when combined with attenuated total reflection (ATR). They will set up a Spectrum Two FTIR-ATR instrument, on loan from PerkinElmer at the CHRF, train personnel, and use it to acquire spectra from approximately 1,500 isolates from their biobank to identify three clinically important pathogens: Klebsiella, Acinetobacter, and Salmonella. They will assess reproducibility across different users and laboratories on a validation set of 100 sequenced isolates, and finally test whether FTIR can identify pathogens directly in blood to produce more rapid results.

Rose Hayeshi of North-West University in South Africa will test whether humanized mouse models harboring selected gene variants specific to indigenous African populations can be used to identify novel therapeutics that will be effective in this population before advancing into clinical trials. Most medicines are developed and tested in European and Asian populations, which can lead to approved drugs that cause adverse reactions or are ineffective in African populations. Cytochrome P450 (CYP) enzyme allelic variants are common in African populations and may affect drug responses. She will use humanized mouse models expressing CYP2B6 and the CYP2B6*6 allelic variant, which is common in African populations, to test whether they can recapitulate specific drug responses observed in vitro and in humans using physiologically-based pharmacokinetic (PBPK) modeling.

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.

Nicole Stoffel of the University of Oxford in the United Kingdom together with Pattanee Winichagoon of Mahidol University in Thailand will perform a double-blind randomized controlled trial to test whether providing iron-fortified food to iron-deficient women in Thailand improves their immune response to vaccination. Vaccines underperform in low- and middle-income countries, which may be caused by poor nutrition. Iron deficiency is common, and iron may play a key role in adaptive immunity and vaccine response. Preliminary data from their earlier study in Kenya showed that women given intravenous iron one week before a vaccine produced significantly more antibodies. To translate this to low-resource settings, they will perform a trial of 180 women in northeastern Thailand and provide half of them with a wheat-flour-based baked snack fortified with iron for forty days and test its effect on their immune response to two vaccine types: an intramuscular influenza vaccine and an oral typhoid vaccine.

Nitin Baliga of the Institute for Systems Biology in the U.S. together with Google Applied Science will combine systems biology with machine learning and artificial intelligence to accelerate the discovery of more effective and affordable treatments for tuberculosis. Tuberculosis kills 1.5 million people annually, but developing novel treatments is expensive using current methods and complicated by the different physiological states and sub-populations of the causative Mycobacterium tuberculosis. To address this, they will use a new modelling approach that leverages transcriptome data and a novel algorithm to identify more robust protein targets that are valid across bacterial states and populations. These targets will then be screened using DNA-encoded small molecule libraries (DELs), which is lower-cost than traditional high-throughput screens. Screening results will be used to train a machine learning model to identify small molecule compounds with favorable drug-like properties and high probabilities of inhibiting the target. The anti-bacterial activity of selected compounds will then be tested experimentally.

Lye McKinnon of the University of Manitoba in Canada together with Ali Ssetaala of the Uganda Virus Research Institute in Uganda will determine whether nasal mucosal immune responses induced by COVID-19 vaccines and natural infection can help prevent infection and transmission. Although COVID-19 mRNA vaccines effectively prevent severe disease, they are less effective at preventing transmission, which is critical for protecting vulnerable populations particularly against emerging, highly transmissible variants. Boosting nasal immunity may locally inhibit replication of the SARS-CoV-2 virus and thereby limit both infection and transmission. To test this, they will perform a two-site longitudinal study in Winnipeg, Canada and Kampala/Entebbe, Uganda of fully vaccinated individuals with and without breakthrough Omicron infections to determine whether existing nasal immunity is protective. They will also test whether Omicron breakthrough boosts virus-specific IgA and T cell responses in the nasal mucosa, which may further protect against transmission. The results may strengthen the case for nasal-delivered vaccines to better contain the COVID-19 pandemic.

Jesse Gitaka of Mount Kenya University in Kenya in collaboration with David Anderson of Burnet Institute in Australia, will develop a diagnostic device for iron deficiency anemia that is suitable for resource-limited settings. Iron deficiency anemia can cause maternal death, prematurity and stunting. Current diagnostic tests require expensive equipment or are not specific enough to distinguish between the different causes of anemia. They will develop a device that detects the low levels of hemoglobin found in immature red blood cells, called reticulocytes. The device will use magnetic beads and microfluidics to physically separate reticulocytes from whole blood, and then absorbance to measure the red color of hemoglobin and thereby determine levels. They will use samples from healthy donors to develop algorithms that can calculate the amount of hemoglobin per reticulocyte to provide an accurate diagnosis.

Maurício Barretto of Fiocruz in Brazil will integrate COVID-19 data from Brazil into existing harmonized datasets from over 500 million people across the world, to better inform public health strategies. International data on COVID-19 is needed to help lift the world out of the pandemic. However, there is little real-world data from South Asia or Brazil. They will map data from the COVID-19 surveillance database for the State of Bahia, which covers a population of 15 million people, to the common data model known as OMOP, which brings together disparate data into a common format. They will run analytical tools on these mapped data to characterize COVID-19 forms and disease outcomes, to quantify the use of COVID-19 treatments in routine practice and to identify risk factors that can be used to predict disease severity and help better manage patients.

Haroon Hafeez of Shaukat Khanum Memorial Cancer Hospital and Research Centre in Pakistan will integrate COVID-19 data from Pakistan into existing harmonized datasets from over 500 million people across the world, to better inform public health strategies. International data on COVID-19 is needed to help lift the world out of the pandemic. However, there is little real-world data from South Asia or Brazil. They will map the anonymized electronic medical records from over 7.8 million people, including over 20,000 COVID-19 positive patients, from a hospital in Lahore to the common data model known as OMOP, which brings together disparate data into a common format. They will run analytical tools on these mapped data to characterize COVID-19 forms and disease outcomes, to quantify the use of COVID-19 treatments in routine practice and to identify risk factors that can be used to predict disease severity and help better manage patients.

Lyle McKinnon of the University of Manitoba in Canada will test whether a specific type of immune cell known as tissue resident memory T cells, which are found in the nasal cavity during SARS-CoV-2 infection, help limit disease severity and viral replication. The nasal mucosa is the first place in the body that is exposed to the SARS-CoV-2 virus. However, little is known about the local immune response and how this may influence disease progression, which varies dramatically between people. They have developed a nasal sampling protocol and will use it to characterize nasal T cells from COVID-19 positive patients in three sites in Winnipeg, Canada, and Nairobi, Kenya, to see if it correlates with clinical outcomes. They will also compare the activation of these nasal tissue T cells in uninfected individuals before and after SARS-CoV-2 vaccination to determine their role in vaccination-mediated immunity.

Jed Sundwall of Open Imagery Network Inc. in the U.S. will collect and curate high-quality agricultural mapping data from drone imagery in Kenya that has commercial value and can also be openly accessed for public good purposes. High quality and timely geospatial data is often only collected in the commercial sector, which makes it too expensive for the public and philanthropic sectors to access and use to address development challenges. To resolve this, they will develop a minimum viable product to demonstrate the potential for collecting high-quality, annotated agricultural data that has commercial value and can also be openly accessed. The imaging data will be obtained from an approximately 40 square kilometre area, annotated to identify field boundaries and building footprints, and made available through their partner, PLACE, who have digital infrastructure and a data trust for providing commercial licenses.