Immune Therapeutics That Combine Fast-Acting Monoclonal Antibody and a Vaccine for Long-Lasting Protection Against Plasmodium falciparum Malaria
Abstract
The WHO reports more than 600,000 yearly deaths due to Plasmodium falciparum malaria. In addition to highly effective anti-malarial compounds and seasonal chemoprevention, vaccines (RTS,S and R21) have been licensed for the control of malaria in pediatric populations. Despite these advances, P. falciparum is rapidly developing resistance to multiple antimalarial drugs, and vaccine efficacy remains moderate and short-lived. As such, we have proposed a two-component immune intervention for adult, military, and traveler markets. Component 1 will be a fast-acting monoclonal antibody (mAb) against P. falciparum's circumsporozoite protein(CSP), while component 2 will be a longer-lasting tobacco mosaic virus-based vaccine displaying the immunodominant CSP NPNA epitope. In the first year, we have concentrated on development of component 1, a monoclonal antibody optimized for longer half-life. During the primary screening and down selection of our first candidate, mAb 317 was found to have off-target binding; consequently, we proceeded with another candidate, mAb 311, for the half-life selection studies. Half-life mutants of mAb 311 were produced and screened using in vitro assays and were observed to retain wild-type antigen binding with improved FcRn binding dynamics. The in vivo studies to determine the half-life of the mAb 311 component are underway. In parallel, development of the component 2 vaccine for cGMP large-scale manufacture is almost complete. The overall project progress is satisfactory.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2023
- Accession Number
- AD1223429
Entities
People
- Sheetij Dutta
Organizations
- Geneva Foundation