Background: Although there has been major progress in reducing the global malaria burden, this decline has recently plateaued. There are still over 200 million cases annually, exacerbated by the impact of COVID-19. An effective vaccine would be a key weapon to eliminate malaria by interfering with the rapid spread of parasites throughout a population. As such, the development of transmission-blocking vaccines is a primary goal of WHO and Gates Foundation, highlighted in the Malaria Vaccine Roadmap. Transmission-blocking vaccines are designed to target an essential biological bottleneck in the malaria life cycle by generating antibodies that can block parasite transmission from humans to mosquitoes. When a mosquito feeds on an infected person, whole blood containing antibodies and transmission stage parasites is ingested. Antibodies of the right functional properties that specifically target gametocytes can inhibit parasite development within the mosquito and prevent their subsequent transmission to humans. However, major knowledge gaps in our understanding of how antibodies block transmission represents a critical roadblock to vaccine development.
Methods: Here, we assessed antibody responses in samples from a unique experimental P. falciparum infection of malaria-naïve Australian adults designed to induce transmission stage parasites. This innovative approach enables the study of immunity upon a single defined infection without the influence of prior malaria exposure. We measured serum antibody levels and functional antibody mechanisms (complement fixation and Fc receptor binding) at multiple time points concurrent with existing clinical data on mosquito transmission collected during the study.
Results/Conclusions: Using recombinant transmission stage antigens that we expressed, we detected high levels of IgG and IgM in the majority of serum samples tested at each time point. However, there was little cytophillic subclasses, IgG1 and IgG3 measured towards these key antigens which resulted in limited functional antibody activity observed. Further, we performed mathematical modelling to determine whether antibody levels correlated with mosquito transmission data. Our findings have major implications to further understand how the acquired human immune response potentially interrupt the transmission of malaria and accelerate the development of transmission-blocking vaccines crucial for malaria elimination.