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Biology subjects

Oludada, O. E.

Publications and source records attributed to Oludada, O. E..

2 recordsLinked to original sources
bioRxiv2023

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

Memory B cells (MBCs) formed over the individuals lifetime constitute nearly half of the adult peripheral blood B cell repertoire in humans. To assess their response to novel antigens, we tracked the origin and followed the differentiation paths of MBCs in the early anti-S response to mRNA vaccination in SARS-CoV-2-naive individuals on single-cell and monoclonal antibody level. Newly generated and pre-existing MBCs differed in their differentiation paths despite similar levels of SARS-CoV-2 and common corona virus S-reactivity. Pre-existing highly mutated MBCs showed no signs of germinal center re-entry and rapidly developed into mature antibody secreting cells (ASCs). In contrast, newly generated MBCs derived from naive precursors showed strong signs of antibody affinity maturation before differentiating into ASCs. Thus, although pre-existing human MBCs have an intrinsic propensity to differentiate into ASCs, the quality of the anti-S antibody and MBC response improved through the clonal selection and affinity maturation of naive precursors. HighlightsO_LImRNA vaccination of SARS-CoV-2 naive individuals recruits naive and pre-existing MBCs with similar levels of S-reactivity into the response C_LIO_LIS-reactive naive but not pre-existing MBCs undergo affinity maturation C_LIO_LIS-reactive pre-existing MBCs dominate the early ASC response independent of their antigen affinity C_LIO_LIHigh-affinity S-reactive MBCs and ASCs develop over time and originate from affinity matured naive precursors C_LI

immunology↗
bioRxiv2023

Molecular and functional properties of human Plasmodium falciparum CSP C-terminus antibodies

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 -thrombospondin repeat (-TSR) domain. Specificity for the polymorphic Th2R/Th3R but not the conserved RII+ region in the -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--TSR antibody response that support exclusion of the PfCSP C terminus from malaria vaccine designs.

immunology↗