Matthew DeLisa of Cornell University in the U.S. will create a cell-free synthetic biology platform for low-income settings that produces thermostable polysaccharide-based conjugate vaccines against diarrheal pathogens upon the addition of water to a single tube. Half-a-million children under age five die each year from diarrhea and dysentery, the majority in low- and middle-income countries. Two major causes of bacterial diarrhea are enterotoxigenic E. coli (ETEC) and Shigella strains. Conjugate vaccines combine multiple antigens into one vaccine to increase its activity. However, they require a complex manufacturing process, living cells, and refrigerated storage, which limit their application in developing countries. They will develop the materials and methods for manufacturing thermostable anti-diarrheal vaccines in single tubes that only require the addition of water just ahead of administration. The tubes will contain a plasmid that can express an FDA-approved carrier protein, along with selected O-antigen-polysaccharides from ETEC or Shigella strains, and an enzyme that can conjugate the two via glycosylation, all within a freeze-dried pellet. Following development, they will test the safety, scalability and portability of the vaccines, and characterize their ability to generate effective antibodies that can kill the bacteria. The system is expected to reduce conjugate vaccine costs, and its modular nature will facilitate expansion to other vaccine-preventable diseases.

Jessica Craig of the Center for Disease Dynamics, Economics and Policy in the U.S. will use existing food distribution networks in low-income countries to publicize the importance of vaccination and inform caregivers when, where, and how to access local vaccine services by printing them on food labels, food and water carrying tools, and receipts. They will test whether their approach can improve vaccination rates using one rural and one urban area each in Kenya and in the Central African Republic. They will map their food distribution systems and health service clinics and consult local healthcare workers on the design of vaccine information materials to reach both literate and illiterate populations. They will evaluate the number of caregivers interacting with the materials using surveys in clinics, as well as the change in vaccination rate before and after a six-month period with materials in circulation. The approach is relatively simple and cost-effective because it leverages an existing network with a wide audience, and requires no additional work from frontline healthcare workers. It is also adaptable to any setting with a food distribution network, and can be expanded to deliver other types of health information.

Aaron Jenkins of the University of Sydney in Australia will combine genomics approaches with physical chemistry to identify the organisms and environmental factors in riverbeds that support the survival and spread of the bacterium, Salmonella enterica serovar Typhi, which causes typhoid. Aquatic environments are a major reservoir of typhoid, but how the bacteria survive in these conditions is unclear, making it difficult to prevent the disease spreading to humans. They hypothesize that S. Typhi survive in biofilms associated with sediments in riverbeds, and that the composition of this niche promotes its ability to infect humans. To test this, they will sample aquatic biofilms from areas of high, low, and zero typhoid incidence in Fiji, and identify the microbial communities supporting S. Typhi survival using antibody capture and metagenomics. They will also use fluorescence in situ hybridization to determine the spatial organization of S. Typhi in multispecies biofilms. In addition, they will analyze the composition of the sediments and soil of the riverbeds, and the nutrients being taken up by resident fish and crustaceans. By combining these results with their epidemiological data, they can identify the ecological niches that support high typhoid incidence, which will help develop and guide intervention strategies to block transmission to humans.

Ernest Darhok of Broadreach in South Africa will use mobile technology to improve access to child immunization services for populations living on the Kenya-Uganda border and help ensure all children are fully vaccinated. Refugee populations living in cross-border settings and migrant communities are particularly difficult to cover because of limited access, poor coordination across borders, and lack of efficient tracking. They have been using a human-centered approach to understand what these populations need to vaccinate their children, and have pilot tested the use of near-field communication cards with an immunization application that holds a child’s vaccination and health data for caregivers, which they can also use to plan more convenient appointments. This card can then be viewed and updated by health workers on both sides of the border using a mobile system. They will extend this pilot study to a wider population in Kenya and Uganda to evaluate the effect on vaccination rates against polio, and apply machine learning methods to better forecast vaccination needs at cross-border facilities to avoid stocks running out. They will obtain user feedback at all stages to help improve their approach.