Preclinical development of a stabilized RH5 virus-like particle vaccine that induces improved antimalarial antibodies

Lloyd D.W. King; David Pulido; Jordan R. Barrett; Hannah Davies; Doris Quinkert; Amelia M. Lias; Sarah E. Silk; David J. Pattinson; Ababacar Diouf; Barnabas G. Williams; Kirsty McHugh; Ana Rodrigues; Cassandra A. Rigby; Veronica Strazza; Jonathan Suurbaar; Chloe Rees-Spear; Rebecca A. Dabbs; Andrew S. Ishizuka; Yu Zhou; Gaurav Gupta; Jing Jin; Yuanyuan Li; Cecilia Carnrot; Angela M. Minassian; Ivan Campeotto; Sarel J. Fleishman; Amy R. Noe; Randall S. MacGill; C. Richter King; Ashley J. Birkett; Lorraine A. Soisson; Carole A. Long; Kazutoyo Miura; Rebecca Ashfield; Katherine Skinner; Mark R. Howarth; Sumi Biswas; Simon J. Draper

doi:10.1016/j.xcrm.2024.101654

Preclinical development of a stabilized RH5 virus-like particle vaccine that induces improved antimalarial antibodies

Lloyd D.W. King, David Pulido, Jordan R. Barrett, Hannah Davies, Doris Quinkert, Amelia M. Lias, Sarah E. Silk, David J. Pattinson, Ababacar Diouf, Barnabas G. Williams, Kirsty McHugh, Ana Rodrigues, Cassandra A. Rigby, Veronica Strazza, Jonathan Suurbaar, Chloe Rees-Spear, Rebecca A. Dabbs, Andrew S. Ishizuka, Yu Zhou, Gaurav GuptaJing Jin, Yuanyuan Li, Cecilia Carnrot, Angela M. Minassian, Ivan Campeotto, Sarel J. Fleishman, Amy R. Noe, Randall S. MacGill, C. Richter King, Ashley J. Birkett, Lorraine A. Soisson, Carole A. Long, Kazutoyo Miura, Rebecca Ashfield, Katherine Skinner, Mark R. Howarth, Sumi Biswas, Simon J. Draper

Department of Biomolecular Sciences

Weizmann Institute of Science

Research output: Contribution to journal › Article › peer-review

Abstract

Plasmodium falciparum reticulocyte-binding protein homolog 5 (RH5) is a leading blood-stage malaria vaccine antigen target, currently in a phase 2b clinical trial as a full-length soluble protein/adjuvant vaccine candidate called RH5.1/Matrix-M. We identify that disordered regions of the full-length RH5 molecule induce non-growth inhibitory antibodies in human vaccinees and that a re-engineered and stabilized immunogen (including just the alpha-helical core of RH5) induces a qualitatively superior growth inhibitory antibody response in rats vaccinated with this protein formulated in Matrix-M adjuvant. In parallel, bioconjugation of this immunogen, termed “RH5.2,” to hepatitis B surface antigen virus-like particles (VLPs) using the “plug-and-display” SpyTag-SpyCatcher platform technology also enables superior quantitative antibody immunogenicity over soluble protein/adjuvant in vaccinated mice and rats. These studies identify a blood-stage malaria vaccine candidate that may improve upon the current leading soluble protein vaccine candidate RH5.1/Matrix-M. The RH5.2-VLP/Matrix-M vaccine candidate is now under evaluation in phase 1a/b clinical trials.

Original language	English
Article number	101654
Journal	Cell Reports Medicine
Volume	5
Issue number	7
DOIs	https://doi.org/10.1016/j.xcrm.2024.101654
State	Published - 16 Jul 2024

All Science Journal Classification (ASJC) codes

General Biochemistry,Genetics and Molecular Biology

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King, L. D. W., Pulido, D., Barrett, J. R., Davies, H., Quinkert, D., Lias, A. M., Silk, S. E., Pattinson, D. J., Diouf, A., Williams, B. G., McHugh, K., Rodrigues, A., Rigby, C. A., Strazza, V., Suurbaar, J., Rees-Spear, C., Dabbs, R. A., Ishizuka, A. S., Zhou, Y., ... Draper, S. J. (2024). Preclinical development of a stabilized RH5 virus-like particle vaccine that induces improved antimalarial antibodies. Cell Reports Medicine, 5(7), Article 101654. https://doi.org/10.1016/j.xcrm.2024.101654

@article{67e92ac61e52422fbc1e4a46aae84f08,

title = "Preclinical development of a stabilized RH5 virus-like particle vaccine that induces improved antimalarial antibodies",

abstract = "Plasmodium falciparum reticulocyte-binding protein homolog 5 (RH5) is a leading blood-stage malaria vaccine antigen target, currently in a phase 2b clinical trial as a full-length soluble protein/adjuvant vaccine candidate called RH5.1/Matrix-M. We identify that disordered regions of the full-length RH5 molecule induce non-growth inhibitory antibodies in human vaccinees and that a re-engineered and stabilized immunogen (including just the alpha-helical core of RH5) induces a qualitatively superior growth inhibitory antibody response in rats vaccinated with this protein formulated in Matrix-M adjuvant. In parallel, bioconjugation of this immunogen, termed “RH5.2,” to hepatitis B surface antigen virus-like particles (VLPs) using the “plug-and-display” SpyTag-SpyCatcher platform technology also enables superior quantitative antibody immunogenicity over soluble protein/adjuvant in vaccinated mice and rats. These studies identify a blood-stage malaria vaccine candidate that may improve upon the current leading soluble protein vaccine candidate RH5.1/Matrix-M. The RH5.2-VLP/Matrix-M vaccine candidate is now under evaluation in phase 1a/b clinical trials.",

author = "King, \{Lloyd D.W.\} and David Pulido and Barrett, \{Jordan R.\} and Hannah Davies and Doris Quinkert and Lias, \{Amelia M.\} and Silk, \{Sarah E.\} and Pattinson, \{David J.\} and Ababacar Diouf and Williams, \{Barnabas G.\} and Kirsty McHugh and Ana Rodrigues and Rigby, \{Cassandra A.\} and Veronica Strazza and Jonathan Suurbaar and Chloe Rees-Spear and Dabbs, \{Rebecca A.\} and Ishizuka, \{Andrew S.\} and Yu Zhou and Gaurav Gupta and Jing Jin and Yuanyuan Li and Cecilia Carnrot and Minassian, \{Angela M.\} and Ivan Campeotto and Fleishman, \{Sarel J.\} and Noe, \{Amy R.\} and MacGill, \{Randall S.\} and King, \{C. Richter\} and Birkett, \{Ashley J.\} and Soisson, \{Lorraine A.\} and Long, \{Carole A.\} and Kazutoyo Miura and Rebecca Ashfield and Katherine Skinner and Howarth, \{Mark R.\} and Sumi Biswas and Draper, \{Simon J.\}",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors",

year = "2024",

month = jul,

day = "16",

doi = "10.1016/j.xcrm.2024.101654",

language = "الإنجليزيّة",

volume = "5",

journal = "Cell Reports Medicine",

issn = "2666-3791",

publisher = "Cell Press",

number = "7",

}

King, LDW, Pulido, D, Barrett, JR, Davies, H, Quinkert, D, Lias, AM, Silk, SE, Pattinson, DJ, Diouf, A, Williams, BG, McHugh, K, Rodrigues, A, Rigby, CA, Strazza, V, Suurbaar, J, Rees-Spear, C, Dabbs, RA, Ishizuka, AS, Zhou, Y, Gupta, G, Jin, J, Li, Y, Carnrot, C, Minassian, AM, Campeotto, I, Fleishman, SJ, Noe, AR, MacGill, RS, King, CR, Birkett, AJ, Soisson, LA, Long, CA, Miura, K, Ashfield, R, Skinner, K, Howarth, MR, Biswas, S & Draper, SJ 2024, 'Preclinical development of a stabilized RH5 virus-like particle vaccine that induces improved antimalarial antibodies', Cell Reports Medicine, vol. 5, no. 7, 101654. https://doi.org/10.1016/j.xcrm.2024.101654

TY - JOUR

T1 - Preclinical development of a stabilized RH5 virus-like particle vaccine that induces improved antimalarial antibodies

AU - King, Lloyd D.W.

AU - Pulido, David

AU - Barrett, Jordan R.

AU - Davies, Hannah

AU - Quinkert, Doris

AU - Lias, Amelia M.

AU - Silk, Sarah E.

AU - Pattinson, David J.

AU - Diouf, Ababacar

AU - Williams, Barnabas G.

AU - McHugh, Kirsty

AU - Rodrigues, Ana

AU - Rigby, Cassandra A.

AU - Strazza, Veronica

AU - Suurbaar, Jonathan

AU - Rees-Spear, Chloe

AU - Dabbs, Rebecca A.

AU - Ishizuka, Andrew S.

AU - Zhou, Yu

AU - Gupta, Gaurav

AU - Jin, Jing

AU - Li, Yuanyuan

AU - Carnrot, Cecilia

AU - Minassian, Angela M.

AU - Campeotto, Ivan

AU - Fleishman, Sarel J.

AU - Noe, Amy R.

AU - MacGill, Randall S.

AU - King, C. Richter

AU - Birkett, Ashley J.

AU - Soisson, Lorraine A.

AU - Long, Carole A.

AU - Miura, Kazutoyo

AU - Ashfield, Rebecca

AU - Skinner, Katherine

AU - Howarth, Mark R.

AU - Biswas, Sumi

AU - Draper, Simon J.

PY - 2024/7/16

Y1 - 2024/7/16

N2 - Plasmodium falciparum reticulocyte-binding protein homolog 5 (RH5) is a leading blood-stage malaria vaccine antigen target, currently in a phase 2b clinical trial as a full-length soluble protein/adjuvant vaccine candidate called RH5.1/Matrix-M. We identify that disordered regions of the full-length RH5 molecule induce non-growth inhibitory antibodies in human vaccinees and that a re-engineered and stabilized immunogen (including just the alpha-helical core of RH5) induces a qualitatively superior growth inhibitory antibody response in rats vaccinated with this protein formulated in Matrix-M adjuvant. In parallel, bioconjugation of this immunogen, termed “RH5.2,” to hepatitis B surface antigen virus-like particles (VLPs) using the “plug-and-display” SpyTag-SpyCatcher platform technology also enables superior quantitative antibody immunogenicity over soluble protein/adjuvant in vaccinated mice and rats. These studies identify a blood-stage malaria vaccine candidate that may improve upon the current leading soluble protein vaccine candidate RH5.1/Matrix-M. The RH5.2-VLP/Matrix-M vaccine candidate is now under evaluation in phase 1a/b clinical trials.

AB - Plasmodium falciparum reticulocyte-binding protein homolog 5 (RH5) is a leading blood-stage malaria vaccine antigen target, currently in a phase 2b clinical trial as a full-length soluble protein/adjuvant vaccine candidate called RH5.1/Matrix-M. We identify that disordered regions of the full-length RH5 molecule induce non-growth inhibitory antibodies in human vaccinees and that a re-engineered and stabilized immunogen (including just the alpha-helical core of RH5) induces a qualitatively superior growth inhibitory antibody response in rats vaccinated with this protein formulated in Matrix-M adjuvant. In parallel, bioconjugation of this immunogen, termed “RH5.2,” to hepatitis B surface antigen virus-like particles (VLPs) using the “plug-and-display” SpyTag-SpyCatcher platform technology also enables superior quantitative antibody immunogenicity over soluble protein/adjuvant in vaccinated mice and rats. These studies identify a blood-stage malaria vaccine candidate that may improve upon the current leading soluble protein vaccine candidate RH5.1/Matrix-M. The RH5.2-VLP/Matrix-M vaccine candidate is now under evaluation in phase 1a/b clinical trials.

UR - http://www.scopus.com/inward/record.url?scp=85198325719&partnerID=8YFLogxK

U2 - 10.1016/j.xcrm.2024.101654

DO - 10.1016/j.xcrm.2024.101654

M3 - مقالة

SN - 2666-3791

VL - 5

JO - Cell Reports Medicine

JF - Cell Reports Medicine

IS - 7

M1 - 101654

ER -

Preclinical development of a stabilized RH5 virus-like particle vaccine that induces improved antimalarial antibodies

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