邢唷>? HJ?G欹€ 餜B/bjbj84xx* 814e$? Z1\1\1\1\1\1\1??Z\1-\1`?Z1Z1?0纔V鯼]:?F1?0??\??00?0@\1\1??  : D桍N1 xvz顅h孴D崺R啒遅Target Diseases and PathogensThis RFP is focused on identifying new interventions in a small set of diseases of relevance to global health, considering strategic alignment with other funders and current investments within the NSFC and the Gates Foundation. Consequently, only proposals addressing these specific indications will be considered.VaccinesWhat we are looking forThe goal of this challenge is to solicit novel concepts and candidates for vaccines that can serve as transformative tools in the efforts to prevent, control or eliminate diseases of our interest. We are particularly interested in approaches to induce unnatural immunity to pathogens to achieve long-lasting immunity across multiple strains, species and/or sub-species, utilizing recent advances made in structural biology, bioinformatics and molecular immunology. Our ultimate goal is to enable a path to move the best vaccine concepts and candidates into clinical development. The scope of vaccine concepts could include ideas specific to the subset of global health pathogens described below, or broad, paradigm-shifting concepts in vaccinology, should they also have potential applicability to those specific pathogens.Target pathogens:Human immunodeficiency virus only approaches that aimed at providing sustained protection will be consideredMycobacterium tuberculosisA few of the many options to be considered include:Applications of new knowledge of structure-based immunogen design.New approaches to target common antigenic components shared by multiple strains that may evolve over time and/or multiple species or sub-speciesNovel vaccine concepts that can prevent infection, and block transmissionNovel vaccine concepts, targets and constructs inspired by new understanding about the mechanism by which a targeted organism induces protective immunity by the human hostNew vaccine concepts that target specific tissue or cell types for appropriate induction of local and systemic immunityNovel vaccines designed specifically for populations with high disease burden or risk of infectionNew experimental systems or models for rapidly testing vaccines and predicting their efficacyWe will not consider funding for:Projects not relevant to the diseases listed aboveIdentification of antigens without preliminary proof or hypothesis that developing such antigens radically improves protective efficacyProjects targeting molecular pathways targeted by currently available antigens or adjuvants currently in clinical developmentVaccine concepts not based on an explicit hypothesis or rationale for improved performance over those candidates currently in developmentApproaches that represent incremental improvements to conventional solutionsBasic studies of pathogen or human biology without a clear component that tests the potential for translation into specific and practical health solutionsTherapeutics:What we are looking for:With this topic we also seek to explore new therapeutic options to treat infectious diseases and other conditions that disproportionately burden those living in low-resource settings. We are particularly interested in approaches that would target specific pathogen populations that are either bottlenecks in the pathogen抯 life-cycle or that are significant contributors to disease or transmission, but may be difficult to treat with current agents. Areas of focus include: exploiting novel sources of chemical diversity not typically found in conventional small molecule libraries, including novel chemical approaches to the manipulation and optimization of complex molecules and natural products; development and prosecution of screening approaches that target pathogens in a realistic environment; and taking advantage of recent scientific and technical advances for target identification, validation, and deconvolution.Target Diseases:TuberculosisNew agents or approaches with the potential for shortening treatment durationMalariaPlasmodium falciparum and Plasmodium vivaxLiver-stage and gametocyte-active agents, and multi-stage active compoundsDiarrheal Disease in infants caused by:Cryptosporidium hominisCryptosporidium parvumA few of the many possible options to be considered include (non-exclusive):Development of assays which allow high-throughput screening of pathogenic organisms under conditions that reflect their natural in vivo environmentApproaches to target typically challenging organisms e.g. intracellular or non-replicating M. tuberculosis, malaria parasite hypnozoites or gametocytesDevelopment of broad and generalizable methods for the optimization of active natural compounds and other complex moleculesWe will not consider funding for:Proposals not directed at one of the pathogens/diseases included in the priority list above.Screening of natural product extracts or other unrefined sources of chemical matterIdentification and prosecution of new drug targets without a clear rationale for how drugs against such targets would fill a gap in our current therapeutic armamentariumBasic research into pathogen biology without a compelling rationale for how such research can be rapidly translated into a new therapeutic discovery approachCommunity@B 镟杖栈杖杖债铡杖諗葒諊誾嚾誾杖杖諊誾諗嚾嚾囌h莚h莚@OJQJh莚h莚@OJQJh莚h莚@OJQJh莚h莚@堷OJQJh莚h莚@堽OJQJh莚h莚@堹OJQJh莚h莚@?OJQJh莚h莚OJQJh8whPY^CJOJQJaJh杶hPY^5丆JOJQJaJ-@B~z UpxnI$ & FWDa$gd莚m$$ & FdとWDa$gdPY^m$$ & FdとWDa$gd莚m$gd莚gd莚gd莚gdPY^ Uo箬箬坭舞坭污链璐鄞凌篡篡璐坭篡篡枸璐坭鄞鄞坭筵戳坭坭ㄨ滆滆ㄨh莚h莚6丱JQJhPY^CJOJQJaJh莚h莚@OJQJh莚h莚@堼OJQJh莚h莚@OJQJh莚h莚@?OJQJh莚h莚OJQJh莚h莚@OJQJ<uv箧冁捂倭未袤尜捂钨媪钨钨唯潗儩v悵儛潈恑悵hh@堽OJQJhh@堹OJQJhh@?OJQJhh@OJQJhhOJQJh莚CJOJQJaJh莚h莚@OJQJh莚h莚@堼OJQJh莚h莚OJQJh莚h莚@?OJQJh莚h莚@OJQJh莚h莚@堽OJQJ)uv9:KX$$ & FdとWDa$gdm$$ & FdとWDa$gdm$$ & FdとWDa$gdm$gdgdgdgdPY^$ & FWDa$gd莚m$gd莚9:L{rsvwxy|}箬垠栉捐茶茶茶茶茶摐摐摐摐摐姄湏湏湏渾渳t}h?h忑b@h?h忑b@?h忑bh覻h忑b@堼h覻h忑b@ h覻h忑bhhCJOJQJaJhh6丱JQJhB*CJOJQJaJph$?`hh@OJQJhh@堷OJQJhhOJQJhh@OJQJ-$Ld{\rsF? /"/$/&/$ & F WDa$gd忑bm$gd忑bgdPY^$ & FWDa$gdm$gd$ & FdとWDa$gdm$$ & FdとWDa$gdm$..........".$.&.(.*.,...0.4.6.:.<.>.@.B.D.F.H.J.L.P.R.V.\.^.b.d.h.j.l.n.p.r.t.|.~.€.?????????????/ /"/黝戾苠荀遘逵孱苠铄宇鬻孱宇苠茴遘逵苠苠苠受遘鬻鬻苠苠铄苡铄苠铃藉h忑bhPY^CJOJQJaJh忑bh?h忑b@h?h忑b@h?h忑b@堼h?h忑b@? h覻h忑bUh?h忑b@h?h忑b@堽A based interventions aimed at improving adherence to drug treatment regimens;Development of broad-spectrum antibiotic or antiviral compounds. 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