Potent AMA1-specific human monoclonal antibody against P. vivax Pre-erythrocytic and Blood Stages
Winnicki, A. C.; King, C. L.; Bosch, J.; Malachin, A. N.; Carias, L. L.; Skomorovska-Prokvolit, Y.; Tham, W.-H.; Dietrich, M. H.; Popovici, J.; Roobsoong, W.; Beeson, J. G.; Sattabongkot, J.; Yeoh, L. M.; Opi, D. H.; Feufack-Donfack, L. B.; Orban, A.; Drago, C. L.; McLaine, O. S.; Redinger, K. R.; Jung, N. C.; Baldor, L.
Show abstract
New therapeutics are necessary for preventing Plasmodium vivax malaria due to easy transmissibility and dormancy in the liver that increases the clinical burden due to recurrent relapse. We isolated 12 Pv Apical Membrane Antigen 1 (PvAMA1) specific human monoclonal antibodies from Peripheral Blood Mononuclear Cells of a Pv-exposed individual. PvAMA1 is essential for sporozoite and merozoite invasion, making it a unique therapeutic target. HumAb 826827 blocked the invasion of human erythrocytes using Pv clinical isolates and inhibited sporozoite invasion of human hepatocytes in vitro (IC50 of 0.3 - 3.7 {micro}g/mL). It also significantly reduced liver infection of chimeric FRG-humHep mice in vivo. The crystal structure of rPvAMA1 bound to 826827 shows that 826827 partially occupies the highly conserved hydrophobic groove in PvAMA1 that binds its known receptor, RON2. We have isolated a potent humAb that is isolate-transcendent, blocks both pre-erythrocytic and blood stage infection, and could be a new therapy for Pv.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Pfs48/45 nanobodies block Plasmodium falciparum transmission 97%
- Natural product-mediated reaction hijacking mechanism validates Plasmodium aspartyl-tRNA synthetase as an antimalarial drug target 95%
- Single domain antibodies against enteric pathogen virulence factors are active as curli fiber fusions on probiotic E. coli Nissle 1917 95%
Similar papers in this journal
- A single full-length VAR2CSA ectodomain variant purifies broadly neutralizing antibodies against placental malaria isolates 94%
- Genetic and chemical validation of Plasmodium falciparum aminopeptidase PfA-M17 as a drug target in the hemoglobin digestion pathway 94%
- Structural basis of malaria transmission blockade by a monoclonal antibody to gamete fusogen HAP2 94%
Similar papers in this journal
- Sites of Vulnerability on Ricin B Chain Revealed through Epitope Mapping of Toxin-Neutralizing Monoclonal Antibodies 94%
- Malaria vaccine candidates displayed on novel virus-like particles are immunogenic and induce transmission-blocking activity 93%
- A novel Leishmania infantum reference strain for gene editing and the study of visceral leishmaniasis 93%
Similar papers in this journal
- Plasmodium falciparum Acetyl-CoA Synthetase is essential for parasite intraerythrocytic development and chromatin modification 94%
- Essential bromodomain TcBDF2 as a drug target against Chagas disease 93%
- Heterologous sarbecovirus receptor binding domains as scaffolds for SARS-CoV-2 receptor binding motif presentation 93%
Similar papers in this journal
- A comparative analysis of memory B cell and antibody responses against Plasmodium falciparum merozoite surface protein 1 in children and adults from Uganda 96%
- Use of Epivolve phage display to generate a monoclonal antibody with opsonic activity directed against a subdominant epitope on extracellular loop 4 of Treponema pallidum BamA (TP0326) 93%
- Reduced placental transfer of antibodies against microbial and vaccine antigens in HIV-infected women in Mozambique 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.