Immune responses to the RTS, S/AS01 malaria vaccine candidate: Lessons from human immunology, parasitologic and clinical evaluations

Abstract

RTS, S/AS01 is a preerythrocytic Plasmodium falciparum malaria vaccine that has received a positive European Medicines Agency scientific opinion upon regulatory evaluation after phase 3 demonstration of partial protection against a range of malaria-related endpoints. Immunological investigations suggest a strong association between circulating anti-circumsporozoite antibody concentrations and simultaneous protection against malaria infection, but a predictive protection threshold has not been identified. Activation of CD4+ T cell has also been demonstrated but their exact function remains unclear. Waning immunity is likely related to antibody decay and parasite biology with a very short transit time of sporozoites in the circulation, rather than an intrinsically deficient induction of immune memory. Investigations are ongoing to determine the role of qualitative aspects of the humoral response, the role of other immune cell types and networks, and the interaction between innate and adaptive responses. Results from immunological investigations are reviewed and discussed in light of efficacy evaluations against malaria in controlled human malaria infection studies and studies in conditions of natural malaria exposure.