Abstract
Development of a malaria vaccine remains a critical priority to decrease clinical disease and mortality and facilitate eradication. Accordingly, RTS,S, a protein-subunit vaccine, has completed phase III clinical trials and confers ~30% protection against clinical infection over 4 years. Whole-attenuated-sporozoite and viral-subunit vaccines induce between 20% and 100% protection against controlled human malaria infection, but there is limited published evidence to date for durable, high-level efficacy (>50%) against natural exposure. Importantly, fundamental scientific advances related to the potency, durability, breadth and location of immune responses will be required for improving vaccine efficacy with these and other vaccine approaches. In this Review, we focus on the current understanding of immunological mechanisms of protection from animal models and human vaccine studies, and on how these data should inform the development of next-generation vaccines. Furthermore, we introduce the concept of using passive immunization with monoclonal antibodies as a new approach to prevent and eliminate malaria.
Highlights
Development of a malaria vaccine remains a critical priority to decrease clinical disease and mortality and facilitate eradication
Natural immunity against malaria develops against the blood stage of infection, thereby providing protection against clinical disease; adults remain susceptible to repeated infections, suggesting that there is little or no natural immunity developed against the preerythrocytic stages, i.e., to the parasite in the liver[2,3,4,5,6]
These findings with rodent Plasmodium parasites were confirmed in human studies showing that the bites of hundreds to thousands of irradiated P. falciparum–infected mosquitoes protected subjects after a controlled human malaria infection (CHMI)[17,18]
Summary
The life cycle of malaria infection and the analysis of immunity to malaria has led to the development of several vaccine approaches (summarized in Table 1 and Fig. 1). Subunit vaccines based on DNA and viral vectors have been developed to induce cell-mediated immunity and eliminate infection in the liver. Most efficacy studies in humans have been performed with preerythrocytic vaccines to target the asymptomatic stage of infection and either prevent infection or decrease clinical disease Overall, both scientific and clinical progress have been made with a variety of vaccines, none of the current approaches are sufficiently effective for long-term sterile protection. Both scientific and clinical progress have been made with a variety of vaccines, none of the current approaches are sufficiently effective for long-term sterile protection In this Review, we focus on how the magnitude, quality, breadth and location of immune responses affect protection at different stages of P. falciparum infection. Nature Immunology | VOL 19 | NOVEMBER 2018 | 1199–1211 | www.nature.com/natureimmunology
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