Evaluating Complement-Mediated Humoral Immunity to P. falciparum Blood Stages

Understanding mechanisms of immunity that protect from malaria is essential for the development of highly effective vaccines. The merozoite form of the parasite, which invades red blood cells, is an important target of protective immunity (Beeson et al., 2016). Biryukov et al. bring to our attention the potential ability of complement factors to enhance P. falciparum merozoite invasion in vitro (Biryukov et al., 2016). They proposed that i) complement activation at the merozoite surface enhanced the ability of merozoites to bind and invaded RBCs and ii) that antibodies tomerozoite surface protein 1 (MSP1) C-terminal region further enhanced this process. These findings were primarily demonstrated with a murine monoclonal antibody (mAb) to MSP1-19, and some assayswere performedwith samples fromaMSP1-42 phase I vaccine trial in malaria-naïve adults. We wish to add further discussion to the potential relevance of these findings, and how they differ from previously published studies to further understand anti-malarial immunity and pathogenesis. We previously reported that there is no difference in merozoite invasion efficiency in normal, complement active sera compared to heat inactivated, complement inactive human sera in the absence of immune antibodies, even at 80% serum concentrations (Boyle et al., 2015). Further, we reported that complement active serum significantly increases the inhibitory capacity of naturally acquired and vaccine-induced human and rabbit antibodies targeting the merozoite (Boyle et al., 2015). We showed that many antibodies required complement factors for invasion inhibitory activity, and we demonstrated the importance of this mechanism for naturally acquired and vaccine induced human and rabbit antibodies against specific merozoite proteins including the