Clinical formulation development of Plasmodium falciparum malaria vaccine candidates based on Pfs48/45, Pfs230, and PfCSP

Research output: Contribution to journalJournal articleResearchpeer-review

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Clinical formulation development of Plasmodium falciparum malaria vaccine candidates based on Pfs48/45, Pfs230, and PfCSP. / Plieskatt, Jordan; Bang, Peter; Wood, Grith Krøyer; Naghizadeh, Mohammad; Singh, Susheel K.; Jore, Matthijs M.; Theisen, Michael.

In: Vaccine, 16.03.2024, p. 1980-1992.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Plieskatt, J, Bang, P, Wood, GK, Naghizadeh, M, Singh, SK, Jore, MM & Theisen, M 2024, 'Clinical formulation development of Plasmodium falciparum malaria vaccine candidates based on Pfs48/45, Pfs230, and PfCSP', Vaccine, pp. 1980-1992. https://doi.org/10.1016/j.vaccine.2024.02.043

APA

Plieskatt, J., Bang, P., Wood, G. K., Naghizadeh, M., Singh, S. K., Jore, M. M., & Theisen, M. (2024). Clinical formulation development of Plasmodium falciparum malaria vaccine candidates based on Pfs48/45, Pfs230, and PfCSP. Vaccine, 1980-1992. https://doi.org/10.1016/j.vaccine.2024.02.043

Vancouver

Plieskatt J, Bang P, Wood GK, Naghizadeh M, Singh SK, Jore MM et al. Clinical formulation development of Plasmodium falciparum malaria vaccine candidates based on Pfs48/45, Pfs230, and PfCSP. Vaccine. 2024 Mar 16;1980-1992. https://doi.org/10.1016/j.vaccine.2024.02.043

Author

Plieskatt, Jordan ; Bang, Peter ; Wood, Grith Krøyer ; Naghizadeh, Mohammad ; Singh, Susheel K. ; Jore, Matthijs M. ; Theisen, Michael. / Clinical formulation development of Plasmodium falciparum malaria vaccine candidates based on Pfs48/45, Pfs230, and PfCSP. In: Vaccine. 2024 ; pp. 1980-1992.

Bibtex

@article{904a11a3b910429f9ff5ebb360bb7b1b,
title = "Clinical formulation development of Plasmodium falciparum malaria vaccine candidates based on Pfs48/45, Pfs230, and PfCSP",
abstract = "Two malaria transmission-blocking vaccine (TBV) candidates, R0.6C and ProC6C, have completed preclinical development including the selection of adjuvants, Alhydrogel{\textregistered} with or without the saponin based adjuvant Matrix-M{\texttrademark}. Here, we report on the final drug product (formulation) design of R0.6C and ProC6C and evaluate their safety and biochemical stability in preparation for preclinical and clinical pharmacy handling. The point-of-injection stability studies demonstrated that both the R0.6C and ProC6C antigens are stable on Alhydrogel in the presence or absence of Matrix-M for up to 24 h at room temperature. As this is the first study to combine Alhydrogel and Matrix-M for clinical use, we also evaluated their potential interactions. Matrix-M adsorbs to Alhydrogel, while not displacing the > 95 % adsorbed protein. The R0.6C and ProC6C formulations were found to be safe and well tolerated in repeated dose toxicity studies in rabbits generating high levels of functional antibodies that blocked infection of mosquitoes. Further, the R0.6C and ProC6C drug products were found to be stable for minimally 24 months when stored at 2–8 °C, with studies ongoing through 36 months. Together, this data demonstrates the safety and suitability of the L. lactis expression system as well as supports the clinical testing of the R0.6C and ProC6C malaria vaccine candidates in First-In-Human clinical trials.",
keywords = "Drug Product, Formulation, Malaria, Manufacture, Toxicology, Vaccine",
author = "Jordan Plieskatt and Peter Bang and Wood, {Grith Kr{\o}yer} and Mohammad Naghizadeh and Singh, {Susheel K.} and Jore, {Matthijs M.} and Michael Theisen",
note = "Publisher Copyright: {\textcopyright} 2024 The Author(s)",
year = "2024",
month = mar,
day = "16",
doi = "10.1016/j.vaccine.2024.02.043",
language = "English",
pages = "1980--1992",
journal = "Vaccine",
issn = "0264-410X",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Clinical formulation development of Plasmodium falciparum malaria vaccine candidates based on Pfs48/45, Pfs230, and PfCSP

AU - Plieskatt, Jordan

AU - Bang, Peter

AU - Wood, Grith Krøyer

AU - Naghizadeh, Mohammad

AU - Singh, Susheel K.

AU - Jore, Matthijs M.

AU - Theisen, Michael

N1 - Publisher Copyright: © 2024 The Author(s)

PY - 2024/3/16

Y1 - 2024/3/16

N2 - Two malaria transmission-blocking vaccine (TBV) candidates, R0.6C and ProC6C, have completed preclinical development including the selection of adjuvants, Alhydrogel® with or without the saponin based adjuvant Matrix-M™. Here, we report on the final drug product (formulation) design of R0.6C and ProC6C and evaluate their safety and biochemical stability in preparation for preclinical and clinical pharmacy handling. The point-of-injection stability studies demonstrated that both the R0.6C and ProC6C antigens are stable on Alhydrogel in the presence or absence of Matrix-M for up to 24 h at room temperature. As this is the first study to combine Alhydrogel and Matrix-M for clinical use, we also evaluated their potential interactions. Matrix-M adsorbs to Alhydrogel, while not displacing the > 95 % adsorbed protein. The R0.6C and ProC6C formulations were found to be safe and well tolerated in repeated dose toxicity studies in rabbits generating high levels of functional antibodies that blocked infection of mosquitoes. Further, the R0.6C and ProC6C drug products were found to be stable for minimally 24 months when stored at 2–8 °C, with studies ongoing through 36 months. Together, this data demonstrates the safety and suitability of the L. lactis expression system as well as supports the clinical testing of the R0.6C and ProC6C malaria vaccine candidates in First-In-Human clinical trials.

AB - Two malaria transmission-blocking vaccine (TBV) candidates, R0.6C and ProC6C, have completed preclinical development including the selection of adjuvants, Alhydrogel® with or without the saponin based adjuvant Matrix-M™. Here, we report on the final drug product (formulation) design of R0.6C and ProC6C and evaluate their safety and biochemical stability in preparation for preclinical and clinical pharmacy handling. The point-of-injection stability studies demonstrated that both the R0.6C and ProC6C antigens are stable on Alhydrogel in the presence or absence of Matrix-M for up to 24 h at room temperature. As this is the first study to combine Alhydrogel and Matrix-M for clinical use, we also evaluated their potential interactions. Matrix-M adsorbs to Alhydrogel, while not displacing the > 95 % adsorbed protein. The R0.6C and ProC6C formulations were found to be safe and well tolerated in repeated dose toxicity studies in rabbits generating high levels of functional antibodies that blocked infection of mosquitoes. Further, the R0.6C and ProC6C drug products were found to be stable for minimally 24 months when stored at 2–8 °C, with studies ongoing through 36 months. Together, this data demonstrates the safety and suitability of the L. lactis expression system as well as supports the clinical testing of the R0.6C and ProC6C malaria vaccine candidates in First-In-Human clinical trials.

KW - Drug Product

KW - Formulation

KW - Malaria

KW - Manufacture

KW - Toxicology

KW - Vaccine

UR - http://www.scopus.com/inward/record.url?scp=85186213677&partnerID=8YFLogxK

U2 - 10.1016/j.vaccine.2024.02.043

DO - 10.1016/j.vaccine.2024.02.043

M3 - Journal article

C2 - 38388238

AN - SCOPUS:85186213677

SP - 1980

EP - 1992

JO - Vaccine

JF - Vaccine

SN - 0264-410X

ER -

ID: 385127676