Validating Immune Correlates of Protection in Children to Advance Malaria Vaccines
BACKGROUND: Malaria is one of the greatest contributors to childhood mortality, and the development of an efficacious vaccine is urgently needed. RTS,S is the only vaccine to undergo phase III clinical testing and recently commenced pilot implementation in 500,000 African children. While RTS,S is currently the leading malaria vaccine, protective efficacy is only 30-50% and rapidly wanes after vaccination.
GAP: Vaccine development is challenging as we poorly understand the immune mechanisms that confer protection against malaria. Antibodies play a crucial role, but antibody titer does not predict clinical outcome and is not a strong correlate of protection. Our research identified novel antibody mechanisms that target the malaria-causing parasite, and initial findings suggest these responses are associated with protection.
HYPOTHESIS: Specific functional antibody responses induced by the RTS,S malaria vaccine will positively correlate with protection against clinical malaria in children.
METHODS: We will quantify functional antibody responses in RTS,S vaccine trials and validate their association with clinical protection and evaluate the longevity of these responses. Specifically, we will measure the functional ability of antibodies to interact with serum complement and Fcγ receptors that are expressed on immune cells. This will be performed using serum collected from phase IIb and III trials performed in African children (>16,000 samples).
IMPACT: Validated correlates of protection will transform vaccine development, and aid the prioritization of new vaccines or inform improvements to the current RTS,S vaccine. Our approaches could be rapidly adapted into other laboratories to advance malaria vaccines and predict clinical outcomes prior to conducting efficacy studies.