[PubMed] [Google Scholar] Espinosa DA, Gutierrez GM, Rojas-Lopez M, Noe AR, Shi L, Tse SW, Sinnis P, Zavala F. Right here we review current vaccine strategies to accelerate elimination and the potential for novel and innovative approaches to vaccine design through a better understanding of the hostCparasite interaction. Following the reinstatement in 2007 of global malaria eradication as a long-term goal, the malaria eradication research agenda initiative was conceived as a scientific consultative process between funding groups, researchers, and interest groups to identify key knowledge gaps and new tools BI605906 required to move toward elimination and the eventual eradication of malaria. The crux of this strategy was enabling development of strategies and mechanisms to interrupt transmission of malaria, without which eradication would not be achievable. In 2011, a comprehensive R&D agenda was published (www.ploscollections.org/malERA2011; a new updated version will be available soon) in which vaccine development was recognized as a key component, complementing other malaria interventions with the objective of interrupting transmission to bring about the eventual eradication of the parasite species responsible for causing malaria in humans. The MalERA agenda introduced the concept of vaccines to interrupt malaria (parasite) transmission (VIMT), which could potentially incorporate the classical transmission-blocking targets, the sexual/mosquito stages (transmission-blocking vaccine [TBV]); preerythrocytic vaccines that markedly reduce asexual- and transmission-stage prevalence rates; erythrocytic-stage vaccines that reduce asexual parasite and gametocyte densities to impact malaria transmission; and mosquito antigens to disrupt development in the vector. Although the main target product profile (TPP) of a VIMT is to interrupt transmission, an important additional benefit would be to provide protection against malaria symptoms and, ideally, to prevent epidemic spread following reintroduction after elimination. A fundamental principle that underpins the current strategic agenda of VIMT development is that population bottlenecks (i.e., points in the life cycle where parasite numbers are low) constitute weak points where targeted approaches have a greater potential for success. As shown in Figure 1, there are two main opportunities for targeting parasite density bottlenecks: during the early exoerythrocytic phase with sporozoite injection and intrahepatocyte infection and development within the mosquito midgut following uptake of gametocytes. The fewer parasites infecting the host tissues, the reasoning goes, the greater the likelihood that induced immune mediators can prevent onward BI605906 development. This is conceptually attractive as a vaccine strategy to prevent infection. Immunity in this vaccine-induced scenario differs from that of naturally acquired immunity to malaria, which occurs only after several exposures, largely to asexual BI605906 targets, and acts to suppress parasite density and thereby prevent malaria symptoms. Another key advantage of a VIMT approach is a smaller population of parasites subjected to immune selection, reducing the probability of vaccine escape mutants. Naturally acquired immunity does not prevent infection or effect complete destruction of parasites in the host (Hoffman et al. 1987; Doolan et al. 2009). Thus, vaccine strategies focused on recapitulating naturally acquired immunity, via the targeting of asexual-stage antigens, are poorly aligned with the VIMT concept. Open in a separate window Figure 1. Points of intervention of a malaria vaccine to accelerate toward elimination. (life cycle. Areas susceptible to antibody-mediated mechanisms are shown in yellow and cell-mediated mechanisms in blue. This schematic does not account for the exoerythrocytic hypnozoite stage causing relapsing blood-stage infections. RBC, Red blood cell; SPZ, sporozoite. IMPORTANT CONSIDERATIONS FOR PRODUCT DEVELOPMENT OF A VACCINE TO ACCELERATE GLOBAL MALARIA ELIMINATION What Does a Malaria Vaccine Need to Do? The outputs from the MalERA processes, which informed the subsequent updates to the Malaria Vaccine Technology Roadmap (who.int/immunization/topics/malaria/vaccine_roadmap/TRM_update_nov13.pdf), have contributed to the establishment of clear community goals for development of a vaccine to interrupt malaria transmission. The 2013 updated Roadmap acknowledges the need for specific measures to tackle the burden of malaria caused by in some regions. The points below, generally presented in the context of also. In high-intensity transmission areas where malaria is not yet under control, a VIMT would synergize with existing or introduced control programs to move these regions toward elimination. In areas where elimination has previously been achieved, such a vaccine would prevent reestablishment of transmission; and in the event of malaria resurgence (e.g., where previous control efforts have broken Mouse monoclonal to AURKA down [Cohen et al. 2012]), it would provide a safety net to prevent disease and death where naturally acquired immunity has waned (White 2014). This issue is particularly relevant in the light of the spread of anopheline resistance to insecticides and the potential time bomb BI605906 of resistance to artemisinin combination therapies (ACTs) crossing into Africa (Ashley.