As elimination is approached, fewer and fewer infections will occur, perhaps making natural boosting of a protective immune response a less impactful attribute of a product’s TPP. Furthermore, expression in the human increases the possibility that immune selection will lead to the proliferation

of escape mutants. Additional data are therefore needed to support GSK1120212 mw whether endemic boosting should be a critical attribute of an ideal SSM-VIMT. The clinical development plan (CDP) and the basis of regulatory approval for an SSM-VIMT will likely be different from those applied to pre-erythrocytic and blood-stage malaria vaccines due to the methods in which vaccine effect will be established at the level of the community rather than the individual. In 2010, the major points of discussion on CDP/regulatory pathway were on the acceptability to regulatory authorities of a vaccine acting via delayed clinical benefit, the appropriate CDP and regulatory pathway, including the potential need for a cluster randomized trial (CRT), and the required level of efficacy. A learn more critical

outcome of the 2010 MVI TBV workshop was that the US Food and Drug Administration (FDA) indicated that there is no legal bar to prevent a vaccine such as an SSM-TBV from being considered for licensure in the context of their review process. The FDA has the authority to license biological products that are demonstrated to be “safe, pure, and potent” (Section 351 of the Public Health Service Act & Section 505(b) of the Food, Drug, and Cosmetic Act), regardless of whether the disease occurs in the United States [23]. This feedback has encouraged the malaria vaccine development community to consider product development pathways for vaccine approaches exclusively targeting

parasite transmission from human to Montelukast Sodium mosquito. In 2012, moreover, the report on the MALVAC meeting states, “great progress has been made in recent years with a general acceptance in malaria vaccine circles that the issue of community benefits for TBV is not a major hurdle for clinical or regulatory pathways” [24]. The challenge moving forward will be to further define both the CDP and regulatory pathways and seek specific feedback from regulators, such as the FDA, European Medicines Agency, or another stringent regulatory authority. Another important outcome of the VIMT research agenda-setting meetings and consultations was the preliminary definition of two potential clinical development pathways for an SSM-VIMT (Fig. 1). One involves a large-scale, Phase 3 efficacy trial, which, in the case of an SSM-VIMT, has been proposed by regulators to be a CRT to demonstrate vaccine impact on incidence of infection in the community.