Broadly inhibitory antibodies to severe malaria virulence proteins – Nature
Miller, L. H., Baruch, D. I., Marsh, K. & Doumbo, O. K. The pathogenic basis of malaria. Nature 415, 673–679 (2002).
Google Scholar
Lennartz, F., Lavstsen, T. & Higgins, M. K. Towards an anti-disease malaria vaccine. Emerg. Top. Life Sci. 1, 539–545 (2017).
Google Scholar
World Health Organization. World malaria report 2023 (WHO, 2023).
Baruch, D. I. et al. Cloning the P. falciparum gene encoding PfEMP1, a malarial variant antigen and adherence receptor on the surface of parasitized human erythrocytes. Cell 82, 77–87 (1995).
Google Scholar
Smith, J. D. et al. Switches in expression of Plasmodium falciparum var genes correlate with changes in antigenic and cytoadherent phenotypes of infected erythrocytes. Cell 82, 101–110 (1995).
Google Scholar
Su, X. Z. et al. The large diverse gene family var encodes proteins involved in cytoadherence and antigenic variation of Plasmodium falciparum-infected erythrocytes. Cell 82, 89–100 (1995).
Google Scholar
Petersen, J. E. et al. Protein C system defects inflicted by the malaria parasite protein PfEMP1 can be overcome by a soluble EPCR variant. Thromb. Haemost. 114, 1038–1048 (2015).
Google Scholar
Gillrie, M. R. et al. Diverse functional outcomes of Plasmodium falciparum ligation of EPCR: potential implications for malarial pathogenesis. Cell Microbiol. 17, 1883–1899 (2015).
Google Scholar
Mosnier, L. O. & Lavstsen, T. The role of EPCR in the pathogenesis of severe malaria. Thromb. Res. 141, S46–S49 (2016).
Google Scholar
Obeng-Adjei, N. et al. Longitudinal analysis of naturally acquired PfEMP1 CIDR domain variant antibodies identifies associations with malaria protection. JCI Insight https://doi.org/10.1172/jci.insight.137262 (2020).
Rambhatla, J. S. et al. Acquisition of antibodies against endothelial protein C receptor-binding domains of Plasmodium falciparum erythrocyte membrane protein 1 in children with severe malaria. J. Infect. Dis. 219, 808–818 (2019).
Google Scholar
Turner, L. et al. IgG antibodies to endothelial protein C receptor-binding cysteine-rich interdomain region domains of Plasmodium falciparum erythrocyte membrane protein 1 are acquired early in life in individuals exposed to malaria. Infect. Immun. 83, 3096–3103 (2015).
Google Scholar
Tewey, M. A. et al. Natural immunity to malaria preferentially targets the endothelial protein C receptor-binding regions of PfEMP1s. mSphere 8, e0045123 (2023).
Google Scholar
Rask, T. S., Hansen, D. A., Theander, T. G., Gorm, P. A. & Lavstsen, T. Plasmodium falciparum erythrocyte membrane protein 1 diversity in seven genomes-divide and conquer. PLoS Comput Biol. https://doi.org/10.1371/journal.pcbi.1000933 (2010).
Rajan Raghavan, S. S. et al. Endothelial protein C receptor binding induces conformational changes to severe malaria-associated group A PfEMP1. Structure https://doi.org/10.1016/j.str.2023.07.011 (2023).
Google Scholar
Lau, C. K. et al. Structural conservation despite huge sequence diversity allows EPCR binding by the PfEMP1 family implicated in severe childhood malaria. Cell Host Microbe 17, 118–129 (2015).
Google Scholar
Bernabeu, M. et al. Binding heterogeneity of Plasmodium falciparum to engineered 3D brain microvessels is mediated by EPCR and ICAM-1. mBio https://doi.org/10.1128/mBio.00420-19 (2019).
Hudetz, A. G. Blood flow in the cerebral capillary network: a review emphasizing observations with intravital microscopy. Microcirculation 4, 233–252 (1997).
Google Scholar
Moka, S. et al. Blood flow velocity comparison in the eye capillaries and postcapillary venules between normal pregnant and non-pregnant women. Microvasc. Res. 127, 103926 (2020).
Google Scholar
Koutsiaris, A. G. et al. Volume flow and wall shear stress quantification in the human conjunctival capillaries and post-capillary venules in vivo. Biorheology 44, 375–386 (2007).
Google Scholar
Chen, X. et al. Assessment of single-vessel cerebral blood velocity by phase contrast fMRI. PLoS Biol. 19, e3000923 (2021).
Google Scholar
Leech, J. H., Barnwell, J. W., Miller, L. H. & Howard, R. J. Identification of a strain-specific malarial antigen exposed on the surface of Plasmodium falciparum-infected erythrocytes. J. Exp. Med. 159, 1567–1575 (1984).
Google Scholar
Marsh, K. & Howard, R. J. Antigens induced on erythrocytes by P. falciparum: expression of diverse and conserved determinants. Science 231, 150–153 (1986).
Google Scholar
Udeinya, I. J., Miller, L. H., McGregor, I. A. & Jensen, J. B. Plasmodium falciparum strain-specific antibody blocks binding of infected erythrocytes to amelanotic melanoma cells. Nature 303, 429–431 (1983).
Google Scholar
Howard, R. J. et al. Two approximately 300 kilodalton Plasmodium falciparum proteins at the surface membrane of infected erythrocytes. Mol. Biochem. Parasitol. 27, 207–223 (1988).
Google Scholar
Doolan, D. L., Dobano, C. & Baird, J. K. Acquired immunity to malaria. Clin. Microbiol. Rev. 22, 13–36 (2009).
Google Scholar
Nielsen, M. A. et al. Plasmodium falciparum variant surface antigen expression varies between isolates causing severe and nonsevere malaria and is modified by acquired immunity. J. Immunol. 168, 3444–3450 (2002).
Google Scholar
Bull, P. C. et al. Parasite antigens on the infected red cell surface are targets for naturally acquired immunity to malaria. Nat. Med. 4, 358–360 (1998).
Google Scholar
Marsh, K., Otoo, L., Hayes, R. J., Carson, D. C. & Greenwood, B. M. Antibodies to blood stage antigens of Plasmodium falciparum in rural Gambians and their relation to protection against infection. Trans. R. Soc. Trop. Med. Hyg. 83, 293–303 (1989).
Google Scholar
Bull, P. C., Lowe, B. S., Kortok, M. & Marsh, K. Antibody recognition of Plasmodium falciparum erythrocyte surface antigens in Kenya: evidence for rare and prevalent variants. Infect. Immun. 67, 733–739 (1999).
Google Scholar
Otto, T. D. et al. Evolutionary analysis of the most polymorphic gene family in falciparum malaria. Wellcome Open Res. 4, 193 (2019).
Google Scholar
Brazier, A. J., Avril, M., Bernabeu, M., Benjamin, M. & Smith, J. D. Pathogenicity determinants of the human malaria parasite Plasmodium falciparum have ancient origins. mSphere https://doi.org/10.1128/mSphere.00348-16 (2017).
Aleshnick, M., Florez-Cuadros, M., Martinson, T. & Wilder, B. K. Monoclonal antibodies for malaria prevention. Mol. Ther. 30, 1810–1821 (2022).
Google Scholar
Cottrell, C. A. et al. Heterologous prime-boost vaccination drives early maturation of HIV broadly neutralizing antibody precursors in humanized mice. Sci. Transl. Med. 16, eadn0223 (2024).
Google Scholar
Steichen, J. M. et al. Vaccine priming of rare HIV broadly neutralizing antibody precursors in nonhuman primates. Science 384, eadj8321 (2024).
Google Scholar
Xie, Z. et al. mRNA-LNP HIV-1 trimer boosters elicit precursors to broad neutralizing antibodies. Science 384, eadk0582 (2024).
Google Scholar
Schiffner, T. et al. Vaccination induces broadly neutralizing antibody precursors to HIV gp41. Nat. Immunol. 25, 1073–1082 (2024).
Google Scholar
Castro, K. M., Scheck, A., Xiao, S. & Correia, B. E. Computational design of vaccine immunogens. Curr. Opin. Biotechnol. 78, 102821 (2022).
Google Scholar
Kilama, M. et al. Estimating the annual entomological inoculation rate for Plasmodium falciparum transmitted by Anopheles gambiae s.l. using three sampling methods in three sites in Uganda. Malar. J. 13, 111 (2014).
Google Scholar
Kamya, M. R. et al. Malaria transmission, infection, and disease at three sites with varied transmission intensity in Uganda: implications for malaria control. Am. J. Trop. Med. Hyg. 92, 903–912 (2015).
Google Scholar
Mmbando, B. P. et al. A progressive declining in the burden of malaria in north-eastern Tanzania. Malar. J. 9, 216 (2010).
Google Scholar
Bushell, K. M., Sollner, C., Schuster-Boeckler, B., Bateman, A. & Wright, G. J. Large-scale screening for novel low-affinity extracellular protein interactions. Genome Res. 18, 622–630 (2008).
Google Scholar
Gonzales, S. J. et al. A molecular analysis of memory B cell and antibody responses against Plasmodium falciparum merozoite surface protein 1 in children and adults from Uganda. Front. Immunol. 13, 809264 (2022).
Google Scholar
Zajac, P., Islam, S., Hochgerner, H., Lonnerberg, P. & Linnarsson, S. Base preferences in non-templated nucleotide incorporation by MMLV-derived reverse transcriptases. PLoS ONE 8, e85270 (2013).
Google Scholar
Kapteyn, J., He, R., McDowell, E. T. & Gang, D. R. Incorporation of non-natural nucleotides into template-switching oligonucleotides reduces background and improves cDNA synthesis from very small RNA samples. BMC Genomics 11, 413 (2010).
Google Scholar
Liao, H. X. et al. High-throughput isolation of immunoglobulin genes from single human B cells and expression as monoclonal antibodies. J. Virol. Methods 158, 171–179 (2009).
Google Scholar
Alamyar, E., Duroux, P., Lefranc, M. P. & Giudicelli, V. IMGT® tools for the nucleotide analysis of immunoglobulin (IG) and T cell receptor (TR) V-(D)-J repertoires, polymorphisms, and IG mutations: IMGT/V-QUEST and IMGT/HighV-QUEST for NGS. Methods Mol. Biol. 882, 569–604 (2012).
Google Scholar
Azasi, Y. et al. Infected erythrocytes expressing DC13 PfEMP1 differ from recombinant proteins in EPCR-binding function. Proc. Natl Acad. Sci. USA 115, 1063–1068 (2018).
Google Scholar
Crooks, G. E., Hon, G., Chandonia, J. M. & Brenner, S. E. WebLogo: a sequence logo generator. Genome Res. 14, 1188–1190 (2004).
Google Scholar
Gonzales, S. J. et al. Naturally acquired humoral immunity against Plasmodium falciparum malaria. Front. Immunol. 11, 594653 (2020).
Google Scholar
Kisalu, N. K. et al. A human monoclonal antibody prevents malaria infection by targeting a new site of vulnerability on the parasite. Nat. Med. 24, 408–416 (2018).
Google Scholar
Turner, L. et al. Severe malaria is associated with parasite binding to endothelial protein C receptor. Nature 498, 502–505 (2013).
Google Scholar
Cham, G. K. et al. A semi-automated multiplex high-throughput assay for measuring IgG antibodies against Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) domains in small volumes of plasma. Malar. J. 7, 108 (2008).
Google Scholar
Skipper Seabold, J. P. Statsmodels: econometric and statistical modeling with Python. In Proc. 9th Python in Science Conference (SCIPY 2010) (eds van der Walt, S. & Millman, J.) 92–96 (scipy, Austin, TX, 2010).
Lennartz, F. et al. Structure-guided identification of a family of dual receptor-binding PfEMP1 that is associated with cerebral malaria. Cell Host Microbe 21, 403–414 (2017).
Google Scholar
Bachmann, A. & Lavstsen, T. Analysis of var gene transcript patterns by quantitative real-time PCR. Methods Mol. Biol. 2470, 149–171 (2022).
Google Scholar
Zheng, Y. et al. In vitro microvessels for the study of angiogenesis and thrombosis. Proc. Natl Acad. Sci. USA 109, 9342–9347 (2012).
Google Scholar
Piatti, L., Howard, C. C., Zheng, Y. & Bernabeu, M. Binding of Plasmodium falciparum-infected red blood cells to engineered 3D microvessels. Methods Mol. Biol. 2470, 557–585 (2022).
Google Scholar
Kabsch, W. Xds. Acta Crystallogr. D 66, 125–132 (2010).
Google Scholar
Evans, P. R. & Murshudov, G. N. How good are my data and what is the resolution? Acta Crystallogr. D Biol. Crystallogr. 69, 1204–1214 (2013).
Google Scholar
Liebschner, D. et al. Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix. Acta Crystallogr. D Struct. Biol. 75, 861–877 (2019).
Google Scholar
Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60, 2126–2132 (2004).
Google Scholar
Croll, T. I. ISOLDE: a physically realistic environment for model building into low-resolution electron-density maps. Acta Crystallogr. D Struct. Biol. 74, 519–530 (2018).
Google Scholar
Pettersen, E. F. et al. UCSF ChimeraX: structure visualization for researchers, educators, and developers. Protein Sci. 30, 70–82 (2021).
Google Scholar
Joosten, R. P., Long, F., Murshudov, G. N. & Perrakis, A. The PDB_REDO server for macromolecular structure model optimization. IUCrJ 1, 213–220 (2014).
Google Scholar
Zheng, S. Q. et al. MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy. Nat. Methods 14, 331–332 (2017).
Google Scholar
Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290–296 (2017).
Google Scholar
Tunyasuvunakool, K. et al. Highly accurate protein structure prediction for the human proteome. Nature 596, 590–596 (2021).
Google Scholar
Abanades, B. et al. ImmuneBuilder: deep-learning models for predicting the structures of immune proteins. Commun. Biol. 6, 575 (2023).
Google Scholar
Afonine, P. V. et al. Real-space refinement in PHENIX for cryo-EM and crystallography. Acta Crystallogr. D Struct. Biol. 74, 531–544 (2018).
Google Scholar
Wang, R. Y. et al. Automated structure refinement of macromolecular assemblies from cryo-EM maps using Rosetta. eLife 5, e17219 (2016).
Google Scholar
Laskowski, R. A. & Swindells, M. B. LigPlot+: multiple ligand–protein interaction diagrams for drug discovery. J. Chem. Inf. Model. 51, 2778–2786 (2011).
Google Scholar
Pettersen, E. F. et al. UCSF Chimera — a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605–1612 (2004).
Google Scholar
Fernandez-Quintero, M. L. et al. Germline-dependent antibody paratope states and pairing specific VH–VL interface dynamics. Front. Immunol. 12, 675655 (2021).
Google Scholar
Chodera, J. D. & Noe, F. Markov state models of biomolecular conformational dynamics. Curr. Opin. Struct. Biol. 25, 135–144 (2014).
Google Scholar
