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.