PATH's novel infusion pump, the RELI Delivery System, was designed to address many of the barriers surrounding access to infusion pumps in LRS: it does not require electricity or a battery, is inexpensive to manufacture and operate, does not require expensive consumables, and has a simple user interface. We will develop a functional prototype and related job aids to share with stakeholders.

PATH seeks to improve access to improved preeclampsia screening in routine antenatal care (ANC) by addressing the need for a low-cost, accurate proteinuria screening tool to replace the protein-only dipstick as the standard used in routine ANC in LRS. PATH is working in collaboration with LifeAssay Diagnostics, Ltd. (South Africa) to develop and support validation of a simple, low-cost protein-to-creatinine ratiometric urine dipstick test and is seeking to demonstrate the feasibility for implementation and use of the test within routine ANC.

This team proposes to develop and test an innovative microarray patch to deliver a combination of antibiotics for the treatment of neonatal sepsis. An easy-to-use, less-invasive, affordable delivery method for amoxicillin and gentamicin could expand access to lifesaving outpatient antibiotic treatment for infants with severe infection during the neonatal period.

Drawing on 10 years of experience developing and delivering essential newborn care training, this project will develop 3D games using an iterative co-design process in UK and Kenya so it excites users and addresses needs and preferences. This project will explore incentives for learning and develop data capture tools to understand who is playing as well as where and when they are playing. This project will also design a test of the effectiveness of our training in Kenya, explore how to extend the approach to maternal care and plan for dissemination and testing.

Ling Ye of Emory University in the U.S., working with Lu Lu of Shanghai Medical College, Fudan University in China, will design a potent HIV vaccine using selected sequences of one of the virus's envelope proteins to trigger the production of broadly neutralizing antibodies. This has been problematic due to the diversity of the viral envelope glycoprotein and its glycosylation shield which prevent the immune system from recognizing it. The membrane-proximal external region (MPER) of the viral envelope protein has been identified as an attractive target for inducing neutralizing antibodies and they have fused it with another viral protein to form a chimera that can partly neutralize infection. They will build on this result by modifying the structure of the MPER to stabilize it in a more active conformation and by fusing it with slightly different viral proteins that can then be immunized altogether. They will evaluate whether this vaccine strategy further stimulates broadly neutralizing antibody production and can fully neutralize HIV in several animal models.

José Castillo of Univercells in Belgium will create a compact low-cost and automated vaccine manufacturing platform by integrating three new technologies to produce more affordable vaccines at around 0.15USD per dose. Vaccine doses are generally 1-10USD most of which is due to inefficient production and high manufacturing costs including the need for major infrastructure. This relatively high cost prohibits their widespread use particularly in developing countries with limited funds. Starting with an inactivated poliovirus vaccine they will design and develop a compact high cell density bioreactor that concentrates vaccine production and high affinity capture membranes to streamline purification. They will house the technologies in a compact series of isolators that can be accommodated in a smaller laboratory space and perform pilot testing at a manufacturer's site to evaluate productivity and analyze purity and concentration of the vaccine.

Tarit Mukhopadhyay of University College London in the United Kingdom will develop a manufacturing platform to reduce the production costs of recombinant protein vaccines. Current manufacturing procedures involve serial batch operations in large complex facilities requiring highly trained operators and extensive testing and are inefficient and costly. They will build a platform that integrates and automates key steps to reduce labor costs and capital expenditure and improves product design and control procedures to reduce quality control requirements. Their aim is to maximize the number of doses with the minimal starting material leading to recombinant subunit vaccines at 0.15USD per dose rather than the current costs of several USD per dose. They will develop their approach initially using a rotavirus vaccine candidate.

Pamela Schnupf of Paris Descartes University in France will develop an oral vaccine to prevent infectious diarrhea in children by engineering a non-pathogenic bacteria to express pathogen molecules that can be safely delivered in bacterial spores. Diarrheal disease caused largely by Shigella and enterotoxigenic Escherichia coli is a major cause of morbidity and mortality in children under five years of age in low-resource settings. Segmented filamentous bacterium (SFB) is non-pathogenic and normally colonizes the human gut during infancy and stimulates the immune system to protect against infections. They will establish methods to genetically engineer SFB to express selected antigens from enterotoxigenic E.coli and test whether it can stimulate an immune response and protect against infection using established mouse models.

Qian Gao of Shanghai Medical College Fudan University in China, working with Clif Barry of The National Institute of Allergy and Infectious Diseases in the U.S., will support a clinical trial to shorten the treatment time for tuberculosis (TB) from six months to four months by helping to identify predictive biomarkers in individuals that only require the shorter treatment. Shortening treatment when possible will substantially reduce costs and the emergence of drug resistance which is a major barrier to eradicating this deadly disease. The phase 2b clinical trial will recruit 620 TB patients at multiple clinics in South Africa and China who will be monitored for disease burden by PET/CT scans and diagnostic assays during treatment and will supply blood and sputum samples for testing. He will analyze RNA and inflammatory markers in serum samples from the Chinese trial participants to identify more robust biomarkers for predicting shorter treatments. He will also determine the strains of the causative Mycobacterium tuberculosis the source of any reinfection (relapse or new infection) and the presence of drug resistant bacteria in these patients and how these link with treatment duration and disease outcome.

One of the reasons oxygen therapy is not reaching the many thousands of babies and children it could save is due to the fact that electricity is not always available in small health facilities. To address this problem, this team has successfully developed FREO2, an electricity-free oxygen concentrator which runs on the energy from water flowing in a nearby stream, and which requires no fuel. This project will enable a major field trial in a health center in Western Uganda, where the design for this innovation will be refined in close collaboration with the health workers.

Michael Schrader of Vaxess Technologies Inc. in the U.S. will develop a microneedle patch that stabilizes vaccines and can deliver multiple doses through the skin at defined times thereby reducing cost waste and the need for repeat immunizations. Vaccinations delivered intradermally via microneedles are at least as effective as intramuscular delivery via injection but reduce the requirement for needles and trained health workers. The patch uses a silk fibroin protein that protects the vaccine against high temperatures removing the need for cold storage and controls the timing of release through the skin. They will refine the material for delivering two doses of inactivated poliovirus vaccine evaluate its safety and activity in animal models and optimize the manufacturing process to ensure reduced costs.