CIS43LS + L9LS

**CIS43LS + L9LS** is a combination of two long-acting monoclonal antibodies (mAbs) designed for malaria prevention by targeting the circumsporozoite protein (CSP) on *Plasmodium falciparum* sporozoites. **CIS43LS** and **L9LS** bind with high affinity to conserved junctional and nearby repeat regions of CSP, respectively, neutralizing sporozoites to prevent liver-stage infection without requiring Fc effector functions for protection in preclinical models. Engineered with LS mutations in the Fc region to extend half-life (e.g., ~56-80 days for CIS43LS), they provide potent, durable prophylaxis; L9LS shows superior potency over CIS43LS in preclinical studies, and both have demonstrated efficacy individually in clinical trials against controlled human malaria infection (CHMI) and natural exposure. Developed by the National Institutes of Health (NIH), this combination is under evaluation for synergistic malaria prevention, potentially complementing vaccines like R21/Matrix-M.