CIS43LS

CIS43LS is a long-acting human IgG1 monoclonal antibody developed for the prevention of Plasmodium falciparum malaria. It works by targeting the highly conserved junctional NPDP epitope of the P. falciparum circumsporozoite protein, which is essential for hepatocyte infection and parasite motility[3][4]. ## Development and Structure CIS43LS was originally isolated from a clinical trial participant who had received an attenuated P. falciparum whole-sporozoite vaccine[1][3]. The antibody was then modified to extend its efficacy and half-life through two site-directed mutagenesis substitutions at amino acid residues N457S and M451L (termed "LS") in the Fc region[3][4]. ## Clinical Trials and Efficacy The monoclonal antibody has shown promising results in clinical trials: - In a Phase 2 trial in Mali involving 369 adults, CIS43LS demonstrated high efficacy in preventing malaria infection. The high dose (40 mg/kg) was 88.2% effective at preventing infection over a 24-week period, while the lower dose (10 mg/kg) was 75% effective[1]. - A Phase 1 trial (VRC 612) showed that CIS43LS was effective even at lower doses and when administered subcutaneously. The study found that doses as low as 5 mg/kg (both intravenously and subcutaneously) provided complete protection against controlled human malaria infection[2][6]. - The antibody has demonstrated the ability to provide high levels of malarial prophylaxis for 8 weeks, with potential additional protection for up to 6 months[3][4]. ## Administration Routes CIS43LS can be administered through both intravenous (IV) and subcutaneous (SC) routes, with both showing effectiveness in clinical trials[2][6]. For subcutaneous administration, participants received 2-4 injections based on weight, in the abdomen and separated by at least 2 inches[2]. ## Safety Profile Clinical trials have consistently shown that CIS43LS is safe and well-tolerated across different dosage levels[1][2][6]. No serious adverse events were reported in the studies. ## Future Directions Research is ongoing to optimize the dose and administration route of CIS43LS for different populations. The successful results from these trials suggest that monoclonal antibodies may transform malaria prevention in endemic regions, particularly for vulnerable populations such as infants, children, and pregnant women[1][5].

Other names

CIS43LSCIS-43LSCIS 43LS