Malaria affects more than 3 billion people in 95 countries, with an estimated 
mortality rate of 400,000 per year. The female Anopheles spp mosquito most 
commonly transmits malaria, and the main burden of disease is due to Plasmodium 
falciparum. The most abundant antigen on the sporozoite surface is the 
Plasmodium falciparum circumsporozoite protein (PfCSP). PfCSP is required for 
parasite development and attachment to host hepatocytes. The first potential 
protein vaccine, RTS,S/ASO1, consists of a recombinant fusion antigen based on 
PfCSP. Initial findings from a phase 3 trial of RTS,S/ASO1 were promising but 
resulted in recommendations for further evaluation in large-scale trials. R21, a 
circumsporozoite protein-based vaccine, combined with an adjuvant, Matrix-M 
(MM), was recently evaluated in a phase 2 investigational study in children 
between 5-17 months of age in Burkina Faso. The R21/MM candidate vaccine 
resulted in high titers of malaria-specific antibodies. On August 26, 2021, the 
findings from a phase 1 trial on a new monoclonal antibody to PfCSP, CIS43LS, 
showed that a single dose of the CIS43LS monoclonal antibody resulted in 
protection against malaria. These new findings have implications for the 
seasonal control of malaria in endemic regions and a possible future role in 
public health strategies to eliminate malaria. This Editorial aims to provide 
the background to developing and evaluating the new malaria vaccines that target 
PfCSP, including the first monoclonal antibody vaccine to malaria.