Development of monoclonal antibody-mediated interventions to combat malaria

Fast-Track proposals will be accepted. Direct-to-Phase II proposals will not be accepted. Number of anticipated awards: 1-3 Budget (total costs): Phase I: up to $300,000 for up to 1 year; Phase II: up to $1,500,000 for up to 3 years. Background According to the World Malaria Report 2020, progress towards malaria control and elimination appears to be slowing in recent years. Although a moderately efficacious vaccine (RTS,S/AS01 [MosquiRix ] has been made available for pilot implementation in selected African countries, novel immunization approaches to combat malaria are still urgently needed. It has been demonstrated previously that polyclonal sera from malaria-exposed individuals could be used to confer protection against malaria in recipients. Research in animal models has also shown that passive transfer of monoclonal antibodies (mAbs) can protect against malaria infection. Recently, passive immunization using mAbs either as immunotherapy or preexposure prophylaxis has been explored for other infectious diseases, such as SARS-CoV-2, HIV or RSV, and has demonstrated promising feasibility both preclinically and clinically. If passive immunization with mAbs or mAb-based interventions against malaria similarly demonstrates promising clinical feasibility, it could be incorporated into public health program strategies, such as for seasonal malaria prophylaxis, prophylaxis for pregnant women or for migrant workers entering malarious areas, or outbreak control, thus enhancing global malaria control and elimination efforts. The availability of well-characterized and appropriately designed mAbs will not only support development of mAb-based immune prophylaxis or immunotherapy strategies but could also provide credentialing of vaccine antigen(s) and necessary tools for rational immunogen design for active immunization approaches. Project Goals The overall goal of this solicitation is to develop mAb or mAb-based candidates for malaria prevention or treatment. The scope of the research can range from product candidate discovery or optimization to preclinical process development leading to IND filing. Applicants may propose to establish initial proof-of-concept data in animals, conduct preclinical process development or production of mAb(s) or mAb-based candidates to combat Plasmodium falciparum or P. vivax malaria by targeting one or more life cycle stages (i.e., pre-erythrocytic, asexual blood, or sexual stages). Proposals to address innovative potential uses for novel indications (e.g., prevention of malaria relapse, overcoming or prevention of emergence or spread of antimalarial drug resistance, etc.) are also encouraged. Phase I activities may include but are not limited to: Identification, construction, optimization/refinement, and/or evaluation (e.g., biophysical, epitope mapping, etc.) of novel mAbs and mAb-based product candidates (e.g., mAb-conjugates), and technology platforms (e.g., viral vectorencoded mAb); Establishment of preliminary process development to demonstrate technical feasibility; Demonstration of potential efficacy and/or safety of the proposed candidates either by in vitro functional assays or in animal models; Phase II activities may include but are not limited to: Preclinical process development leading to IND filing; activities may include formulation studies, process scale up, stability studies, analytical assay development, cGMP production, or GLP safety assessment; Further preclinical assessment in animal models, including non-human primates; Stability testing to support product stability program for later stages of product development. This SBIR will not support: The design and conduct of clinical trials (see https://grants.nih.gov/policy/clinical-trials/definition.htm for the NIH definition of a clinical trial).