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Recent malaria vaccine trials in endemic areas have yielded disparate results compared to studies conducted in non-endemic areas. A workshop was organized to discuss the differential pre-erythrocytic stage malaria vaccine (Pre-E-Vac) efficacies and underlying protective immunity under various conditions. It was concluded that many factors, including vaccine technology platforms, host genetics or physiologic conditions, and parasite and mosquito vector variations, may all contribute to Pre-E-Vac efficacy. Cross-disciplinary approaches are needed to decipher the multi-dimensional variables that contribute to the observed vaccine hypo-responsiveness. The malaria vaccine community has an opportunity to leverage recent advances in immunology, systems vaccinology, and high dimensionality data science methodologies to generate new clinical datasets with unprecedented levels of functional resolution as well as capitalize on existing datasets for comprehensive and aggregate analyses. These approaches would help to unlock our understanding of Pre-E-Vac immunology and to translate new candidates from the laboratory to the field more predictably.

In March 2013, the National Institute of Allergy and Infectious Diseases and the Bill and Melinda Gates Foundation co-sponsored a meeting entitled "Schistosomiasis Elimination Strategy and Potential Role of a Vaccine in Achieving Global Health Goals" to discuss the potential role of schistosomiasis vaccines and other tools in the context of schistosomiasis control and elimination strategies. It was concluded that although schistosomiasis elimination in some focal areas may be achievable through current mass drug administration programs, global control and elimination will face several significant scientific and operational challenges, and will require an integrated approach with other, additional interventions. These challenges include vector (snail) control; environmental modification; water, sanitation, and hygiene; and other future innovative tools such as vaccines. Defining a clear product development plan that reflects a vaccine strategy as complementary to the existing control programs to combat different forms of schistosomiasis will be important to develop a vaccine effectively.

Pedro Alonso and colleagues introduce the Malaria Eradication Research Agenda (malERA) initiative and the set of articles published in this PLoS Medicine Supplement that distill the research questions key to malaria eradication., The interruption of malaria transmission worldwide is one of the greatest challenges for international health and development communities. The current expert view suggests that, by aggressively scaling up control with currently available tools and strategies, much greater gains could be achieved against malaria, including elimination from a number of countries and regions; however, even with maximal effort we will fall short of global eradication. The Malaria Eradication Research Agenda (malERA) complements the current research agenda—primarily directed towards reducing morbidity and mortality—with one that aims to identify key knowledge gaps and define the strategies and tools that will result in reducing the basic reproduction rate to less than 1, with the ultimate aim of eradication of the parasite from the human population. Sustained commitment from local communities, civil society, policy leaders, and the scientific community, together with a massive effort to build a strong base of researchers from the endemic areas will be critical factors in the success of this new agenda.

PERSPECTIVE • JID 2009:200 (1 December) • 1639 Although it is an ancient and historical disease, malaria persists unabated in many parts of the world today. An estimated 3.3 billion people—approximately one-half of the world’s population living in 109 coun­ tries—are at risk of contracting this seri­ ous and often life-threatening disease. Ma­ laria accounts for ∼250 million clinical cases and nearly 1 million deaths each year, the great majority of which occur in chil­ dren younger than 5 years of age and in young, pregnant women. Malaria influ­ ences the social and economic well-being of societies in affected areas, draining scarce health and human resources, inter­ fering with educational achievement, and causing persistent economic disadvan­ tage [1]. In October 2007, Bill and Melinda Gates issued a call for a renewed effort at achieving global malaria eradication [2]. Whereas elimination involves ridding lo­ cal and regional populations of the para

During the course of establishing infection in a susceptible host, obligate intracellular parasites evade host defence mechanisms before, during and after entry into host cells. Before entry they circumvent the lytic activity of the complement cascade, during cell entry they avoid being killed by toxic oxygen metabolites and after entry they escape nonoxidative killing mechanisms such as degradation by lysosomal hydrolases. Different intracellular parasites, exemplified here by Leishmania spp, Trypanosoma cruzi and Toxoplasma gondii, undermine host defences at each step by various strategies that ultimately ensure their targeting to, and survival in, an appropriate intracellular compartment.

New sources of funding have revitalized efforts to control malaria. An effective vaccine would be a tremendous asset in the fight against this devastating disease and increasing financial and scientific resources are being invested to develop one. A few candidates have been tested in Phase I and II clinical trials, and several others are poised to begin trials soon. Some studies have been promising, and others disappointing. It is difficult to compare the results of these clinical trials; even independent trials of the same vaccine give highly discrepant results. One major obstacle in evaluating malaria vaccines is the difficulty of diagnosing clinical malaria. This analysis evaluates the impact of diagnostic error, particularly that introduced by microscopy, on the outcome of efficacy trials of malaria vaccines and make recommendations for improving future trials.

A multiple antigen peptide (MAP) malaria vaccine containing minimal Plasmodium falciparum circumsporozoite protein repeat epitopes was assessed for safety and immunogenicity in volunteers of known class II genotypes. The MAP/alum/QS-21 vaccine formulation elicited high levels of parasite-specific antibodies in 10 of 12 volunteers expressing DQB1*0603, DRB1*0401, or DRB1*1101 class II molecules. In contrast, volunteers of other HLA genotypes were low responders or nonresponders. A second study of 7 volunteers confirmed the correlation of class II genotype and high responder phenotype. This is the first demonstration in humans that a peptide vaccine containing minimal T and B cell epitopes composed of only 5 amino acids (N, A, V, D, and P) can elicit antibody titers comparable to multiple exposures to irradiated P. falciparum-infected mosquitoes. Moreover, the high-responder phenotypes were predicted by analysis of peptide/HLA interactions in vitro, thus facilitating the rational design of epitope-based peptide vaccines for malaria, as well as for other pathogens.

Achieving a malaria-free world presents exciting scientific challenges as well as overwhelming health, equity, and economic benefits. WHO and countries are setting ambitious goals for reducing the burden and eliminating malaria through the “Global Technical Strategy” and 21 countries are aiming to eliminate malaria by 2020. The commitment to achieve these targets should be celebrated. However, the need for innovation to achieve these goals, sustain elimination, and free the world of malaria is greater than ever. Over 180 experts across multiple disciplines are engaged in the Malaria Eradication Research Agenda (malERA) Refresh process to address problems that need to be solved. The result is a research and development agenda to accelerate malaria elimination and, in the longer term, transform the malaria community’s ability to eradicate it globally., The malERA Refresh Consultative Panel on Health Systems and Policy Research summarize a research and development agenda to accelerate malaria elimination and eradicate globally.