Abstract
For decades, research and development toward malaria vaccine has prioritized infections caused by Plasmodium falciparum, since it is the species responsible for the most severe cases of malaria, which results in a comparatively smaller number of studies devoted to Plasmodium vivax. This disparity is due to complexities inherent in the biology of P. vivax, including the formation of hypnozoites in the pre-erythrocytic phase, difficulties in establishing robust in vitro culture systems, and the absence of fully representative experimental models. Among the antigens investigated for vaccine formulations, the Plasmodium vivax circumsporozoite surface protein (PvCSP) stands out for its immunogenic potential and the partial protection observed in preclinical studies. However, clinical trials with PvCSP-based vaccines have not yet demonstrated a consistent protective response. This review aims to show a historical overview of the studies that have evaluated the potential of vaccines based on the PvCSP protein, as well as to explore the innovative approaches that have been investigated in the last decade to overcome the challenges and advance the development of an effective vaccine against malaria caused by P. vivax.