The main objective therefore of EBOVAC 2 is to provide extensive and robust data on the safety, immunogenicity and efficacy of the Ad26.ZEBOV and MVA-BN-Filo vaccine. This will be done by: 1. Carrying out translational studies to link vaccine elicited immune responses in humans to protection from Ebola in vaccinated non-human primates (via WP4) 2. Carrying out Phase II trials in African and European volunteers in 6 countries, four in Africa and two in the EU with an overall target enrolment of approximately 1,500 subjects. Given the compressed nature of this development program, the Phase II studies will be conducted in parallel with the planned Phase III study (EBOVAC1). The phase II studies will be placebo-controlled and will be conducted in locations where it is possible to perform carefully controlled safety studies (via WP2). 3. Evaluating the use of the vaccine in special population groups, such as children (ages 1-17 years), the elderly (ages 50-65) and individuals infected with HIV, to confirm safety and immunogenicity. It is intended that Phase II trials will begin as soon as safety data are available from Phase I trials (via WP2). 4. Monitoring and characterising immune response to the proposed vaccine (via WP3). 5. Boosting the capacity of African centres, staff and infrastructure in preparation for Phase III studies and communicating and disseminating widely the results of EBOVAC2 as they become available to all key stakeholders (via WP6). 6. Contributing all data to the Central Information Repository for use by other Ebola programme projects as well as the wider community (via WP5).

Malaria is one of the deadliest diseases transmitted by Anopheles gambiae in West Africa. As no vaccine is yet available and no direct control of breeding sites possible, the main option to control malaria is to prevent vector-host contact. This is mainly achieved by using insecticide-treated bed-nets (ITNs) and indoor residual house spraying. Presently the only recommended insecticides for treating mosquito nets are pyrethroids (PYRs) because of their excito-repellent properties, efficacy at low-dose, and good tolerance in humans. However, the extensive and rapid roll out of ITNs in the last decade selected PYR resistance in A. gambiae from the whole sub-Saharan Africa. This constitutes a major hindrance to malaria control. The goal of the AlterNET project is to acquire pertinent information concerning the risk of using insecticides from two other insecticide classes (organophosphates [OPs] and carbamates [CXs]), which have been proposed to work around PYR resistance. As the dynamics of resistance is driven by the biological and population characteristics of the considered species and by the intensity of the selection pressure it receives, the project is organized along two main axes: 1. Understand OP and CX selection pressures. As no global health control program uses OP or CX for mosquito control in Africa, the question is open to clearly identify the origin of selection pressures that have selected the ace-1 alleles presently observed in A. gambiae. These pressures probably result from environmental pollutions generated by human activities that require insect control such as agriculture and/or domestic personal protection. They need to be clarified, both in terms of insecticide usages (quantity, frequency) and locations. To identify OP and CX pressures from all origins in distinct ecological areas, we will: (a) investigate the professional practices of market gardeners, especially concerning the uses of pesticides, using the concepts and tools developed for "Pharmaceutical anthropology". A precise knowledge of the nature and quantity of pesticides, apprehending the socio-cultural building of decision processes in the choice and practices of insecticide uses will be acquired; (b) monitor resistance of Culex pipiens quinquefasciatus, a mosquito species adapted to a wide range of habitats with a particularly fast response to selection pressure. Data will feed previously developed models for estimating selection pressure. 2. Study the adaptation to OP and CX of A. gambiae populations. Some A. gambiae s.s. populations from West Africa have already developed resistance to OP and CX by selection of a single mutation in the ace-1 gene (ace-1R) coding the synaptic acetylcholinesterase (AChE1). Recently, a new "duplicated" allele, ace-1D, putting in tandem a wild-type and a resistant copy of ace-1 on the same chromosome was detected in Ivory Coast and Burkina Faso. This duplication is suspected to improve mosquito fitness while maintaining resistance and could favour resistance spread. We will monitor the distribution of ace-1R and ace-1D alleles in Benin and Burkina Faso, from 2013 to 2015. We will also generate and analyze lab strains carrying these resistance alleles in a similar genetic background to evaluate their impact on mosquito fitness (including behaviour). Population models will be developed and parameterized with the data acquired from field surveys and strain analyses to monitor and predict OP/CX resistance dynamics. The combination of the different investigations concerning An. gambiae and selection pressures along with anthropological data will bring about information about how OP and CX resistance could evolve, may or may not jeopardize malaria control, and possibly could be modified, the ultimate goal of the AlterNET project.