The challenges of a circumsporozoite protein-based malaria vaccine
Deepyan Chatterjee, Ian A. Cockburn
Abstract
INTRODUCTION: circumsporozoite protein (PfCSP) of the malaria parasite. However, protection by RTS,S is incomplete and short-lived. AREAS COVERED: Here we summarize results from recent clinical trials of RTS,S and critically evaluate recent studies that aim to understand the correlates of protective immunity and why vaccine-induced protection is short-lived. In particular, recent systems serology studies have highlighted a key role for the necessity of inducing functional antibodies. In-depth analyses of immune responses to CSP in both mouse models and vaccinated humans have also highlighted difficulties in generating the maintaining high-quality antibody responses. Finally, in recent years biophysical and structural studies of antibody binding to PfCSP have led to a better understanding of how highly potent antibodies can block infection, which can inform vaccine design. EXPERT OPINION: We highlight how both structure-guided vaccine design and a better understanding of the immune response to PfCSP can inform a second generation of PfCSP-based vaccines stimulating a broader range of protective targets within PfCSP.