Awards

Isaac Sseswanyana of the Infectious Diseases Research Collaboration in Uganda will investigate natural anti-parasite immunity to malaria to guide the development of improved malaria vaccines and therapeutics. Natural anti-parasite immunity is observed in malaria endemic regions in adults and infants who control parasitemia at low levels without developing symptoms, in the latter group likely due at least in part to the transfer of effective maternal antibodies. They will use existing samples from two longitudinal studies in Uganda to test the hypothesis that the repertoires, biophysical properties, and functional features of Plasmodium falciparum-specific antibodies are determinants of this natural immunity. They will also identify and characterize malaria-specific T cells that correlate with anti-parasite immunity and focus on evaluating cellular or proteomic predictors of durable anti-parasite antibodies.

Aida Sadikh Badiane of the Universite Cheikh Anta Diop de Dakar in Senegal will use a metabolomics platform to identify cervicovaginal metabolites and inflammatory mediators associated with high-risk human papillomavirus (HPV) infection, which cause the majority of cervical cancer cases, in Senegalese women. Cervical cancer is the leading cause of cancer deaths in women in sub-Saharan Africa. Metabolic and immune markers could enable more effective diagnoses for these diseases than the current methods used in low-resource settings. They will perform a prospective, cross-sectional study on a cohort of 385 women using an untargeted metabolomics platform to identify molecules within the cervicovaginal microenvironment that are predictive of infection and cancer risk. They will also use Luminex assays to evaluate inflammatory molecules and other markers associated with infection, and sequence the L1-HPV gene in the samples to better track the genotypes in Senegal.

Simon Kariuki of the Kenya Medical Research Institute in Kenya will use an antibody platform to characterize children's immune responses to the new malaria vaccine to determine the impact of any accompanying infections. The WHO recently approved a new malaria vaccine that will mainly be deployed in sub-Saharan Africa. During its development, HIV-infected children were found to mount weaker immune responses. Helminth infections, which are prevalent in sub-Saharan Africa, are also suspected to negatively impact vaccine efficacy. To test this, they will use an antibody-dynamics platform to assess the impact of helminths and other current or prior parasitic, bacterial, and viral infections on humoral and cellular immune responses following the 4th dose of the new malaria vaccine in two- to three-year-old children at six hospitals in western Kenya. This will help design more effective deployment strategies such as deworming before vaccination.

Senjuti Saha of the Child Health Research Foundation in Bangladesh will use a single-cell analytics platform to track the immune responses of babies before and after receiving a pneumococcal conjugate vaccine to determine the impact of various factors, including nutritional status and seasonality, on vaccine efficacy. Vaccines have successfully reduced childhood morbidity and mortality; however, their efficacy can be influenced by host factors and extrinsic factors through unknown cellular mechanisms. They will recruit 50 newborns in a rural district north of Dhaka and collect blood and nasopharyngeal swabs before, during and after a routine vaccination series. They will extract peripheral blood mononuclear cells and use them to perform single-cell RNA sequencing to identify cell subtypes and link differential vaccine responses to factors including gestational age, nutritional status and sex.

Abdoulaye Djimde of the University of Sciences, Techniques, and Technologies of Bamako in Mali will use a metabolomics platform to identify biomarkers to detect dormant Plasmodia hypnozoites in a previously malaria-infected individual as a diagnostic method and to screen for new therapeutics. Malaria remains one of the deadliest parasitic diseases in the world, with 95% of deaths occurring in sub-Saharan Africa. Most research focuses on the most prevalent causative parasite, Plasmodium falciparum, but other strains, including P. vivax and P. ovale, are likely to become more dominant. These strains uniquely produce hypnozoites, which can lay dormant for years in the liver where they are undetectable and resistant to treatment. They will generate hypnozoite-containing liver cells in vitro and subject them to metabolomics analysis to identify hypnozoite-associated biomarkers. Candidate biomarkers will then be validated in serum samples from thirty infected individuals.

Laeticia Toe of the Institut de Recherche en Sciences de la Sante in Burkina Faso will use a metabolomics profiling platform to identify new biomarkers that can be used to diagnose environmental enteric dysfunction (EED) in women of reproductive age. EED affects nutrient absorption and immune function and may cause adverse birth outcomes in pregnant women. It is widespread in deprived areas in low- and middle-income settings but is often undiagnosed because the gold-standard diagnostic method requires an invasive procedure by trained personnel. They will determine the prevalence of EED by performing ELISA on existing plasma, serum and stool samples from 80 women of reproductive age living in rural Burkina Faso. They will then apply untargeted metabolomics on the samples to identify biomarkers that can be integrated with inflammatory markers and sequencing data and cross-validated for large-scale diagnoses of EED in women from low-resource settings.