Towards the Knowledge-based Design of Universal Influenza Epitope Ensemble Vaccines

Motivation: Influenza A viral heterogeneity remains a significant threat due to unpredictable antigenic drift in seasonal influenza and antigenic shifts caused by the emergence of novel subtypes. Annual review of multivalent influenza vaccines targets strains of influenza A and B likely to be predominant in future influenza seasons. This does not induce broad, cross protective immunity against emergent subtypes. Better strategies are needed to prevent future pandemics. Cross-protection can be achieved by activating CD8+ and CD4+ T cells against highly-conserved regions of the influenza genome. We combine available experimental data with informatics-based immunological predictions to help design vaccines potentially able to induce cross-protective T-cells against multiple influenza subtypes. Results: To exemplify our approach we designed two epitope ensemble vaccines comprising highlyconserved and experimentally-verified immunogenic influenza A epitopes as putative non-seasonal influenza vaccines; one specifically targets the US population and the other is a universal vaccine. The USA-specific vaccine comprised 6 CD8+ T cell epitopes (GILGFVFTL, FMYSDFHFI, GMDPRMCSL, SVKEKDMTK, FYIQMCTEL, DTVNRTHQY) and 3 CD4+ epitopes (KGILGFVFTLTVPSE, EYIMKGVYINTALLN, ILGFVFTLTVPSERG). The universal vaccine comprised 8 CD8+ epitopes: (FMYSDFHFI, GILGFVFTL, ILRGSVAHK, FYIQMCTEL, ILKGKFQTA, YYLEKANKI, VSDGGPNLY, YSHGTGTGY) and the same 3 CD4+ epitopes. Our USA-specific vaccine has a population protection coverage (portion of the population potentially responsive to one or more component epitopes of the vaccine, PPC) of over 96% and 95% coverage of observed influenza subtypes. The universal vaccine has a PPC value of over 97% and 88% coverage of observed subtypes.

Design of maintenance structures for rural electrification with solar home systems. The case of the Moroccan program.

n decentralised rural electrification through solar home systems, private companies and promoting institutions are faced with the problem of deploying maintenance structures to operate and guarantee the service of the solar systems for long periods (ten years or more). The problems linked to decentralisation, such as the dispersion of dwellings, difficult access and maintenance needs, makes it an arduous task. This paper proposes an innovative design tool created ad hoc for photovoltaic rural electrification based on a real photovoltaic rural electrification program in Morocco as a special case study. The tool is developed from a mathematical model comprising a set of decision variables (location, transport, etc.) that must meet certain constraints and whose optimisation criterion is the minimum cost of the operation and maintenance activity assuming an established quality of service. The main output of the model is the overall cost of the maintenance structure. The best location for the local maintenance headquarters and warehouses in a given region is established, as are the number of maintenance technicians and vehicles required.