A Randomized Trial Assessing the Safety and Immunogenicity of AS01 and AS02 Adjuvanted RTS,S Malaria Vaccine Candidates in Children in Gabon

Background:The malaria vaccine candidate antigen RTS,S includes parts of the pre-erythrocytic stage circumsporozoite protein fused to the Hepatitis B surface antigen. Two Adjuvant Systems are in development for this vaccine, an oil-in water emulsion – based formulation (AS02) and a formulation based on liposomes (AS01).Methods & Principal Findings:In this Phase II, double-blind study (NCT00307021), 180 healthy Gabonese children aged 18 months to 4 years were randomized to receive either RTS,S/AS01E or RTS,S/AS02D, on a 0–1–2 month vaccination schedule. The children were followed-up daily for six days after each vaccination and monthly for 14 months. Blood samples were collected at 4 time-points. Both vaccines were well tolerated. Safety parameters were distributed similarly between the two groups. Both vaccines elicited a strong specific immune response after Doses 2 and 3 with a ratio of anti-CS GMT titers (AS02D/AS01E) of 0.88 (95% CI: 0.68–1.15) post-Dose 3. After Doses 2 and 3 of experimental vaccines, anti-CS and anti-HBs antibody GMTs were higher in children who had been previously vaccinated with at least one dose of hepatitis B vaccine compared to those not previously vaccinated.Conclusions:RTS,S/AS01E proved similarly as well tolerated and immunogenic as RTS,S/AS02D, completing an essential step in the age de-escalation process within the RTS,S clinical development plan

Induction of Plasmodium falciparum-Specific CD4+ T Cells and Memory B Cells in Gabonese Children Vaccinated with RTS,S/AS01E and RTS,S/AS02D

The recombinant circumsporozoite protein (CS) based vaccine, RTS,S, confers protection against Plasmodium falciparum infection in controlled challenge trials and in field studies. The RTS,S recombinant antigen has been formulated with two adjuvant systems, AS01 and AS02, which have both been shown to induce strong specific antibody responses and CD4 T cell responses in adults. As infants and young children are particularly susceptible to malaria infection and constitute the main target population for a malaria vaccine, we have evaluated the induction of adaptive immune responses in young children living in malaria endemic regions following vaccination with RTS,S/AS01(E) and RTS,S/AS02(D). Our data show that a CS-specific memory B cell response is induced one month after the second and third vaccine dose and that CS-specific antibodies and memory B cells persist up to 12 months after the last vaccine injection. Both formulations also induced low but significant amounts of CS-specific IL-2(+) CD4(+) T cells one month after the second and third vaccine dose, upon short-term in vitro stimulation of whole blood cells with peptides covering the entire CS derived sequence in RTS,S. These results provide evidence that both RTS,S/AS01(E) and RTS,S/AS02(D) induced adaptive immune responses including antibodies, circulating memory B cells and CD4(+) T cells directed against P. falciparum CS protein.ClinicalTrials.gov NCT00307021

How Ecosystem Services Knowledge and Values Influence Farmers' Decision-Making

International audienceThe ecosystem services (ES) concept has emerged and spread widely recently, to enhance the importance of preserving ecosystems through global change in order to maintain their benefits for human well-being. Numerous studies consider various dimensions of the interactions between ecosystems and land use via ES, but integrated research addressing the complete feedback loop between biodiversity, ES and land use has remained mostly theoretical. Few studies consider feedbacks from ecosystems to land use systems through ES, exploring how ES are taken into account in land management decisions. To fill this gap, we carried out a role-playing game to explore how ES cognition mediates feedbacks from environmental change on farmers' behaviors in a mountain grassland system. On a close to real landscape game board, farmers were faced with changes in ES under climatic and socio-economic scenarios and prompted to plan for the future and to take land management decisions as they deemed necessary. The outcomes of role-playing game were complemented with additional agronomic and ecological data from interviews and fieldwork. The effects of changes in ES on decision were mainly direct, i.e. not affecting knowledge and values, when they constituted situations with which farmers were accustomed. For example, a reduction of forage quantity following droughts led farmers to shift from mowing to grazing. Sometimes, ES cognitions were affected by ES changes or by external factors, leading to an indirect feedback. This happened when fertilization was stopped after farmers learned that it was inefficient in a drought context. Farmers' behaviors did not always reflect their attitudes towards ES because other factors including topographic constraints, social value of farming or farmer individual and household characteristics also influenced land-management decisions. Those results demonstrated the interest to take into account the complete feedback loop between ES and land management decisions to favor more sustainable ES management