Prabhanshu Tripathi

Abstract Repetitive display of the major repeats of the Plasmodium falciparum circumsporozoite protein (PfCSP) is the basis for two WHO-recommended vaccines: RTS,S/AS01 and R21/Matrix-M. Recently, however, the CIS43 monoclonal antibody that preferentially targets the junctional region of PfCSP has been shown to be highly protective in humans, highlighting its junctional epitope as a key vaccine target.

Monoclonal antibody L9 recognizes the Plasmodium falciparum circumsporozoite protein (PfCSP) and is highly protective following controlled human malaria challenge. To gain insight into its function, we determined cryoelectron microscopy (cryo-EM) structures of L9 in complex with full-length PfCSP and assessed how this recognition influenced protection by wild-type and mutant L9s. Cryo-EM reconstructions at 3.6- and 3.7-Å resolution revealed L9 to recognize PfCSP as an atypical trimer.

Supplemental Figure 1. TLR activation of BMDC resulted in increased CD86 expression. Bone marrow derived dendritic cells (BMDC) were derived from C57BL/6 mice and incubated with TLR ligands for 24 hours. The cells were harvested and stained for flow cytometry analysis as described in Materials and methods. (A) Representative flow cytometry plots for BMDC gating strategy are shown. (B) Histograms show levels of CD86 expression on total CD11c+ BMDC from one representative experiment of two performed.