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. As such, the development of vaccines that specifically block the transmission of malaria is a primary goal of WHO and Gates Foundation. Transmission-blocking vaccines are designed to target an essential biological bottleneck in the malaria lifecycle by generating antibodies that 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. In our study we aim to determine the major targets and function of antibodies, with a key focus on the role of IgM.
Methods: Here, we assessed antibody responses in samples from malaria-exposed children and adults from Kenya. We measured serum antibody levels and functional immune mechanisms (such as complement fixation and activation) and examined their correlation with clinical data available from the study cohorts.
Results/Conclusions: We detected high levels of IgM in serum samples tested from both children and adults. Further we showed that IgM purified from immune sera was capable of fixing and activating human complement. Our findings directly support a key role for IgM in mediating functional immunity that block malaria transmission. 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.