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Passive immunization can be a valuable approach to induce short-term protection (up to 6 months) against malaria for e.g. The concept of passive immunization against malaria is not new 2, but only recently it has been demonstrated that it can induce protection in humans against a controlled malaria infection and prevent onward transmission 3, 4.

Currently, the passive transfer of monoclonal antibodies (mAbs) as a prevention strategy for malaria infections is gaining traction.

Since the gains of the current approaches have levelled off and malaria still causes more than 500,000 deaths annually, controlling and eventually eradicating malaria requires additional strategies 1. Insight that will help deepen our understanding of anti-CSP mAb potency and guide selection of the most promising anti-CSP mAbs for downstream clinical development. By quantitatively assessing motility, we created a valuable tool that can be used for comprehensive assessment of anti-CSP mAb potency.

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In our ex vivo skin explant model, SPZ proved less susceptible to anti-CSP mAbs compared to SPZ in an in vitro environment. In a subset of SPZ (5%), in vitro motility was unaffected by the presence of 2A10 while 3SP2 was able to completely block movement. We found a sevenfold discrepancy between the IC 50M and the binding saturation concentration measured by ELISA, possibly related to the observed shedding of CSP-mAb complexes during SPZ movement. Our assay provided a quantitative measure of mAb parasite-inhibitory capacity through measurement of the half-maximal motility inhibitory concentration (IC 50M) value for anti-CSP mAbs (IC 50M 2A10: 24 nM, IC 50M 3SP2: 71 nM). In this study, we employed a quantitative imaging-based motility assay to quantify the effect of anti-CSP mAbs on SPZ motility, both in vitro and in human skin. Comprehensive assessment of the parasite-inhibitory capacity of anti-CSP monoclonal antibodies (mAbs) is an important step in advancing CSP-based immunization strategies. Circumsporozoite protein (CSP), the most abundant surface protein of SPZ is the leading candidate for passive (and subunit) immunization approaches against malaria.

Antibodies can prevent malaria by neutralizing the infectious Plasmodium falciparum sporozoites (SPZ) before they establish an infection in the liver.

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