Novel single-cell preservation and RNA sequencing technology unlocks field studies for Plasmodium natural infections - Nature

We’re sharing this article early to provide faster access to peer-reviewed, accepted research. It is citable and carries a permanent DOI. This version is subject to further edits and will be replaced automatically by the final Version of Record. All legal disclaimers apply. AbstractPre-erythrocytic malaria vaccines aim to prevent infection at the earliest stage of parasite entry by blocking Plasmodium falciparum sporozoites before hepatocyte invasion, thereby halting progression to symptomatic blood-stage disease. The circumsporozoite protein (CSP), the dominant surface antigen of sporozoites, remains the leading target for pre-erythrocytic vaccine development. Here, we investigated the use of an mRNA vaccine platform to express CSP and examined how antigen localisation influences immunogenicity and protective efficacy. We compared mRNA constructs encoding soluble CSP with versions engineered for membrane anchoring using either a mammalian glycosylphosphatidylinositol (GPI) sequence derived from placental alkaline phosphatase or a heterologous transmembrane (TM) domain from influenza H1N1 haemagglutinin.

We’re sharing this article early to provide faster access to peer-reviewed, accepted research. It is citable and carries a permanent DOI. This version is subject to further edits and will be replaced automatically by the final Version of Record. All legal disclaimers apply. AbstractTransmission of Plasmodium falciparum requires the differentiation of asexual parasites into male and female gametocytes, which undergo extensive cytoskeletal remodeling, assembling a non-canonical subpellicular microtubule (SPMT) network. Using single-particle cryo-electron microscopy, we determined structures of SPMTs isolated from developing gametocytes. Unexpectedly, we identified human hemoglobin as a prominent microtubule-associated factor that binds to P. falciparum SPMTs in a dimeric form rather than the canonical tetramer. Pharmacological perturbation of microtubules and hemoglobin isoform switching experiments demonstrate that this hemoglobin-SPMT association is essential for proper SPMT organization and gametocyte maturation. Together, these findings reveal a strategy by which P.

membership, and when you purchase through links on our site, we may earn an affiliate commission.