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9 results on '"Kumarasingha, Rasika"'

2. A 4-cyano-3-methylisoquinoline inhibitor of Plasmodium falciparum growth targets the sodium efflux pump PfATP4

Author

Gilson, Paul R., Kumarasingha, Rasika, Thompson, Jennifer, Zhang, Xinxin, Penington, Jocelyn Sietsma, Kalhor, Robabeh, Bullen, Hayley E., Lehane, Adele M., Dans, Madeline G., de Koning-Ward, Tania F., Holien, Jessica K., Soares da Costa, Tatiana P., Hulett, Mark D., Buskes, Melissa J., Crabb, Brendan S., Kirk, Kiaran, Papenfuss, Anthony T., Cowman, Alan F., and Abbott, Belinda M.

Published
2019
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4. Transcriptional Memory-Like Imprints and Enhanced Functional Activity in γδ T Cells Following Resolution of Malaria Infection

Author

Kumarasingha, Rasika, primary, Ioannidis, Lisa J., additional, Abeysekera, Waruni, additional, Studniberg, Stephanie, additional, Wijesurendra, Dinidu, additional, Mazhari, Ramin, additional, Poole, Daniel P., additional, Mueller, Ivo, additional, Schofield, Louis, additional, Hansen, Diana S., additional, and Eriksson, Emily M., additional

Published
2020
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5. Human Antibodies that Slow Erythrocyte Invasion Potentiate Malaria-Neutralizing Antibodies

Author

Alanine, Daniel G.W., primary, Quinkert, Doris, additional, Kumarasingha, Rasika, additional, Mehmood, Shahid, additional, Donnellan, Francesca R., additional, Minkah, Nana K., additional, Dadonaite, Bernadeta, additional, Diouf, Ababacar, additional, Galaway, Francis, additional, Silk, Sarah E., additional, Jamwal, Abhishek, additional, Marshall, Jennifer M., additional, Miura, Kazutoyo, additional, Foquet, Lander, additional, Elias, Sean C., additional, Labbé, Geneviève M., additional, Douglas, Alexander D., additional, Jin, Jing, additional, Payne, Ruth O., additional, Illingworth, Joseph J., additional, Pattinson, David J., additional, Pulido, David, additional, Williams, Barnabas G., additional, de Jongh, Willem A., additional, Wright, Gavin J., additional, Kappe, Stefan H.I., additional, Robinson, Carol V., additional, Long, Carole A., additional, Crabb, Brendan S., additional, Gilson, Paul R., additional, Higgins, Matthew K., additional, and Draper, Simon J., additional

Published
2019
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9. Human Antibodies that Slow Erythrocyte Invasion Potentiate Malaria-Neutralizing Antibodies

Author

Alanine, Daniel G W, Quinkert, Doris, Kumarasingha, Rasika, Mehmood, Shahid, Donnellan, Francesca R, Minkah, Nana K, Dadonaite, Bernadeta, Diouf, Ababacar, Galaway, Francis, Silk, Sarah E, Jamwal, Abhishek, Marshall, Jennifer M, Miura, Kazutoyo, Foquet, Lander, Elias, Sean C, Labbé, Geneviève M, Douglas, Alexander D, Jin, Jing, Payne, Ruth O, Illingworth, Joseph J, Pattinson, David J, Pulido, David, Williams, Barnabas G, de Jongh, Willem A, Wright, Gavin J, Kappe, Stefan H I, Robinson, Carol V, Long, Carole A, Crabb, Brendan S, Gilson, Paul R, Higgins, Matthew K, and Draper, Simon J

Subjects
Adult, Male, Erythrocytes, Adolescent, Plasmodium falciparum, Protozoan Proteins, Antibodies, Protozoan, Cross Reactions, Rats, Sprague-Dawley, Epitopes, Young Adult, Malaria Vaccines, Animals, Humans, Malaria, Falciparum, Binding Sites, Merozoites, Antibodies, Monoclonal, Middle Aged, Antibodies, Neutralizing, Healthy Volunteers, Rats, HEK293 Cells, Female, Rabbits, Carrier Proteins
Abstract

The Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) is the leading target for next-generation vaccines against the disease-causing blood-stage of malaria. However, little is known about how human antibodies confer functional immunity against this antigen. We isolated a panel of human monoclonal antibodies (mAbs) against PfRH5 from peripheral blood B cells from vaccinees in the first clinical trial of a PfRH5-based vaccine. We identified a subset of mAbs with neutralizing activity that bind to three distinct sites and another subset of mAbs that are non-functional, or even antagonistic to neutralizing antibodies. We also identify the epitope of a novel group of non-neutralizing antibodies that significantly reduce the speed of red blood cell invasion by the merozoite, thereby potentiating the effect of all neutralizing PfRH5 antibodies as well as synergizing with antibodies targeting other malaria invasion proteins. Our results provide a roadmap for structure-guided vaccine development to maximize antibody efficacy against blood-stage malaria. Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

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