Multi-functional antibody profiling for malaria vaccine development and evaluation.

Background: A vaccine would greatly accelerate current global efforts toward malaria elimination. While a partially efficacious vaccine has been achieved for Plasmodium falciparum, a major bottleneck in developing highly efficacious vaccines is a lack of reliable correlates of protection, and the limited application of assays that quantify functional immune responses to evaluate and down-select vaccine candidates in pre-clinical studies and clinical trials.

Methods: In this review, we describe the important role of antibodies in immunity against malaria and detail the nature and functional activities of antibodies against the malaria-causing parasite. We highlight the growing understanding of antibody effector functions against malaria and in vitro assays to measure these functional antibody responses. We discuss the application of these assays to quantify antibody functions in vaccine development and evaluation.

Conclusions: It is becoming increasingly clear that multiple antibody effector functions are involved in immunity to malaria. Therefore, we propose that evaluating vaccine candidates needs to move beyond individual assays or measuring IgG magnitude alone. Instead, vaccine evaluation should incorporate the full breadth of antibody response types and harness a wider range of assays measuring functional antibody responses. We propose a 3-tier approach to implementing assays to inform vaccine evaluation.