Anti-TRAP/SSP2 monoclonal antibodies can inhibit sporozoite infection and enhance protection of anti-CSP monoclonal antibodies

Abstract

Vaccine-induced sterilizing protection from infection with the Plasmodium parasite, the pathogen that causes malaria, will be an essential tool in the fight against malaria as it would prevent both malaria-related disease and transmission. Stopping the relatively small number of parasites injected by the mosquito before they can migrate from the skin to the liver is an attractive goal. Antibody-eliciting vaccines have been used to pursue this objective by targeting the major parasite surface protein present during this stage, the circumsporozoite protein (CSP). While CSP-based vaccines have recently had encouraging success in disease reduction, this was only achieved with extremely high antibody titers and appeared less effective for a complete block of infection. While such disease reduction is important, these results also indicate that further improvements to vaccines based solely on CSP will likely yield diminishing benefits towards the goal of durable, infection-blocking immunity. Here, we show that monoclonal antibodies (mAbs) recognizing the sporozoite protein TRAP/SSP2 across the major protein domains exhibit a range of inhibitory capacity and that these mAbs can augment CSP-based protection despite delivering no sterile protection on their own. Therefore, pursuing a multivalent subunit vaccine immunization is a promising strategy for improving infection-blocking malaria vaccines.

Monoclonal antibodies for malaria prevention

“…A recent manuscript in preprint has shed some light on this and has demonstrated that anti-TRAP mAbs can significantly improve the protective efficacy of anti-CSP mAbs in both rodent models and liver-humanized mice to above 80% at low doses. 68 However, whether this enhancement is additive or synergistic was not addressed and will be critical for determining the utility of such combinations. Together, these data suggest that combinations of PE mAbs may be a pathway to achieving high levels of protection at serum concentrations achievable over extended periods.…”