Malaria, a mosquito-borne disease caused by Plasmodium spp., was responsible for nearly half a million deaths in 2017, with an additional 3.2 billion people at risk of disease. While aggressive insecticide-treated bed-net distribution, mosquito control, and anti-malarial drug distribution programs have significantly reduced mortality associated with the disease, the disease continues to spread nearly unabated, suggesting that a vaccine against this infection is desperately needed. Despite the slow pace of malaria vaccine design, several vaccines have shown promise in the field demonstrating 30?50% protection in field efficacy or Phase 2 trials. Correlates analyses have suggested that both humoral immune responses and cellular immunity may both play critical parts in protection from infection; however, the precise mechanism by which these immune responses synergize to drive immunity may provide the critical insights to advance the design of next-generation vaccines able to provide higher levels of global protection. Moreover, field studies have highlighted the potentially deleterious influence of pre-existing antibodies in endemic regions on vaccine response. Thus, under this proposal we seek to exploit our Systems Serology antibody profiling approach, across a large array of sporozoite/early liver antigens, to define both the correlates of immunity against malaria infection following PfSPZ immunization as well as to define the specific mechanism(s) by which pre-existing antibodies shape the response to vaccination. Ultimately, the results from this study will provide novel insights for the development of next generation vaccines against malaria.
The proposal aims to dissect and define the correlates of immunity that track with protection from malaria infection following irradiated sporozoite vaccination as well as dissect the role of pre-existing immunity in shaping these vaccine-induced immune responses.
