Conference Agenda

Malaria remains a major global health challenge, with substantial morbidity and mortality despite ongoing control efforts. Current vaccines targeting the pre-erythrocytic stage provide only partial and waning protection, highlighting the need for improved strategies. One promising approach is the development of multi-stage vaccines that target different stages of the parasite lifecycle to enhance overall efficacy and durability. Virus-like particles (VLPs) provide an attractive platform for vaccine design due to their ability to present antigens in a highly repetitive and ordered manner, thereby promoting robust immune responses. Increasing evidence suggests that the density of antigens on nanoparticle platforms plays a critical role in shaping immunogenicity. In this study, we explored engineering approaches to optimise antigen display on VLPs and systematically modulate antigen density. We demonstrate that engineered VLPs can maintain structural integrity while accommodating varying levels of antigen presentation. Importantly, increasing antigen density was associated with enhanced antibody responses, supporting the concept that antigen valency is a key determinant of immunogenicity. These findings provide a foundation for the rational design of next-generation nanoparticle vaccines including multi-stage/multi-antigen designs that are currently in progress in our lab.

Malaria remains a major global health challenge due to the complexity of the Plasmodium life cycle, the partial efficacy of current vaccines, and disease severity driven by both parasite factors and host immune responses, including perforin-mediated cytotoxicity. We investigated the impact of treatment timing with a perforin inhibitory compound on disease progression in vaccinated and unvaccinated mice infected with Plasmodium yoelii. Vaccinated mice received killed, whole P. yoelii blood-stage parasites formulated with liposomes and the TLR4 agonist 3D-(6-acyl)-PHAD. Mice were challenged with 10⁵ P. yoelii parasitised red blood cells and treated with a perforin inhibitory compound or vehicle control using two regimens: early (days -1 to 3 post-infection) or late (days 4 to 8 post-infection). Mice were monitored over 26 days. Early perforin inhibitory treatment showed a trend towards reduced parasitaemia and clinical severity; however, these changes were not statistically significant compared with the control groups in either vaccinated or unvaccinated mice. Notably, unvaccinated mice treated with the perforin inhibitory compound exhibited a 6–8 day extension in survival compared to controls, regardless of early or late treatment, although all mice ultimately succumbed to infection. These findings suggest perforin-mediated cytotoxicity contributes to malaria pathology and may be a therapeutic target.