Monoclonal antibody CIS43LS sets the bar for long-acting malaria protection

Monoclonal antibodies (mAbs) targeting Plasmodium falciparum epitopes aim to address gaps in malaria prevention, with potential to profoundly impact high-risk populations. In this issue of the JCI, Tran et al. performed pharmacokinetic and pharmacodynamic analyses on the mAb CIS43LS, which targets a unique conserved hinge region on the sporozoite protein CSP and previously demonstrated a high level of durable protection in controlled human malaria infections. Their findings establish a solid benchmark for mAb protection, demonstrating 80% protection from liver-stage invasion for 4-6 months. A clinical correlate of protection was estimated at antibody levels over 64 μg/mL. Successful protection could also be achieved from subcutaneous injections requiring lower doses. While efficacy of individual mAbs is more straightforward to demonstrate, exploring combination approaches targeting variable regions and diverse effector functions seems prudent to address the problem of evolving microbial pathogens. Combining both mAbs and long-acting malaria drugs may improve efficacy and reduce resistance.