Molecular and functional properties of humanPlasmodium falciparumCSP C-terminus antibodies

Abstract

Human monoclonal antibodies (mAbs) against the central repeat and junction domain of Plasmodium falciparum circumsporozoite protein (PfCSP) have been studied extensively to guide malaria vaccine design compared to antibodies against the PfCSP C terminus. Here, we describe the molecular characteristics and protective potential of a panel of 73 germline and mutated human mAbs against the highly immunogenic PfCSP C-terminal domain. Two mAbs recognized linear epitopes in the C-terminal linker with sequence similarity to repeat and junction motifs, whereas all others targeted conformational epitopes in the α-thrombospondin repeat (α-TSR) domain. Specificity for the polymorphic Th2R/Th3R but not the conserved RII+ region in the α-TSR was associated with IGHV3-21/IGVL3-21 or IGLV3-1 gene usage. Although the C terminus specific mAbs showed signs of more efficient affinity maturation and class-switching compared to anti-repeat mAbs, parasite inhibitory activity was limited to a single C-linker reactive mAb with cross-reactivity to the central repeat and junction. The data provide novel insights in the human anti-C-linker and anti-α-TSR antibody response that support exclusion of the PfCSP C terminus from malaria vaccine designs.

Memory B cells dominate the early antibody-secreting cell response to SARS-CoV-2 mRNA vaccination in naïve individuals independently of their antibody affinity

“…SPR measurements were performed using a Biacore T200 (GE Health-care) instrument docked with Series S Sensor Chip CM5 (GE Healthcare), as previously described 36 . Briefly, anti-human Igκ and Igλ antibodies were immobilized on the chip using an amine coupling-based human antibody Fab capture kit.…”

Development of an anti-Pfs230 monoclonal antibody as a Plasmodium falciparum gametocyte blocker

“…While a plethora of anti-Plasmodium effectors have been developed to block the parasite while it invades the mosquito midgut epithelium or translocates from the midgut to the salivary glands, the molecular targets blocking the parasites at the earlier gametocyte stages remained to be fully identi ed (9)(10)(11)(12)(13). In this study, we focused on developing and producing a gametocyte-stage blocker to target the early infection stages.…”