Clinical formulation development of Plasmodium falciparum malaria vaccine candidates based on Pfs48/45, Pfs230, and PfCSP
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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 journal › Journal article › Research › peer-review
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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