Preclinical development of a monoclonal antibody to prevent P. falciparum malaria

In October 2021, the World Health Organization (WHO) recommended broad use of RTS,S, the world’s first malaria vaccine, in children at risk. Although a significant reduction in malaria disease and deaths is anticipated after implementation of this recommendation, new intervention tools are still needed in fighting against malaria. RTS,S functions primarily by inducing high titer antibodies to the invariant repeat region of the P. falciparum CS protein. Highly potent monoclonal antibodies (mAbs) in protective antisera are likely to be promising tools for malaria intervention. The project team aims to isolate and develop a potent anti-CSP mAb for malaria prevention. The project is enabled by access to a panel of potent anti-CSP mAbs, identified from volunteers who were protected against P. falciparum challenge following immunization with RTS,S. Applying in silico, in vitro, and in vivo methodologies the project team characterized hundreds candidate mAbs and optimize the selected 4 mAbs for enhanced potency and serum stability. After further evaluation for to address potential safety concerns, one final mAb will be advanced to further preclinical and clinical development as a tool for malaria intervention.

The proposed work will start with production and release of a pre-master cell bank for production of the mAb of final selection. The manufacture process for the mAb will be developed and optimized to confirm conditions for production of the mAb lot suitable for GLP toxicity studies, and to enable future scale up production for clinical trial materials. In addition, formulation development will be conducted to enable stability of the mAb at high concentration to accommodate potential subcutaneous injection. The mAb materials produced during the process development and the mAb lot for the GLP toxicity studies will be evaluated in mouse challenge model to confirm protective efficacy. A pre-IND meeting will be conducted with US FDA. We will also conduct IND-enabling GLP-toxicology studies to evaluate repeated dose toxicity and tissue-cross reactivity of the mAb. In parallel, a COGs analysis will be conducted with information on methods of production, product configuration (vial type and size), and a competitive landscape analysis will be conducted with information on mAbs in development for malaria prevention. Finally, an iPDPP will be drafted for alignment clinical, regulatory, manufacturing, and policy strategies for global health deployment of mAbs and alike.

GHIT - Funding details

Product Development

Mar 2022 — Mar 2024

$5.39M

Japan