A randomized first-in-human phase I trial of differentially adjuvanted Pfs48/45 malaria vaccines in Burkinabé adults

Alfred B. Tiono; Jordan L. Plieskatt; Alphonse Ouedraogo; Ben Idriss Soulama; Kazutoyo Miura; Edith C. Bougouma; Mohammad Naghizadeh; Aissata Barry; Jean Baptist B. Yaro; Sem Ezinmegnon; Noelie Henry; Ebenezer Addo Ofori; Bright Adu; Susheel K. Singh; Augustin Konkobo; Karin Lövgren Bengtsson; Amidou Diarra; Cecilia Carnrot; Jenny M. Reimer; Amidou Ouedraogo; Moussa Tienta; Carole A. Long; Issa N. Ouedraogo; Issaka Sagara; Sodiomon B. Sirima; Michael Theisen

doi:10.1172/JCI175707

A randomized first-in-human phase I trial of differentially adjuvanted Pfs48/45 malaria vaccines in Burkinabé adults

Alfred B. Tiono, Jordan L. Plieskatt, Alphonse Ouedraogo, Ben Idriss Soulama, Kazutoyo Miura, Edith C. Bougouma, Mohammad Naghizadeh, Aissata Barry, Jean Baptist B. Yaro, Sem Ezinmegnon, Noelie Henry, Ebenezer Addo Ofori, Bright Adu, Susheel K. Singh, Augustin Konkobo, Karin Lövgren Bengtsson, Amidou Diarra, Cecilia Carnrot, Jenny M. Reimer, Amidou OuedraogoMoussa Tienta, Carole A. Long, Issa N. Ouedraogo, Issaka Sagara, Sodiomon B. Sirima, Michael Theisen

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Abstract

BACKGROUND. Malaria transmission-blocking vaccines aim to interrupt the transmission of malaria from one person to another. METHODS. The candidates R0.6C and ProC6C share the 6C domain of the Plasmodium falciparum sexual-stage antigen Pfs48/45. R0.6C utilizes the glutamate-rich protein (GLURP) as a carrier, and ProC6C includes a second domain (Pfs230-Pro) and a short 36–amino acid circumsporozoite protein (CSP) sequence. Healthy adults (n = 125) from a malaria-endemic area of Burkina Faso were immunized with 3 intramuscular injections, 4 weeks apart, of 30 μg or 100 μg R0.6C or ProC6C each adsorbed to Alhydrogel (AlOH) adjuvant alone or in combination with Matrix-M (15 μg or 50 μg, respectively). The allocation was random and double-blind for this phase I trial. RESULTS. The vaccines were safe and well tolerated with no vaccine-related serious adverse events. A total of 7 adverse events, mild to moderate in intensity and considered possibly related to the study vaccines, were recorded. Vaccine-specific antibodies were highest in volunteers immunized with 100 μg ProC6C-AlOH with Matrix-M, and 13 of 20 (65%) individuals in the group showed greater than 80% transmission-reducing activity (TRA) when evaluated in the standard membrane feeding assay at 15 mg/mL IgG. In contrast, R0.6C induced sporadic TRA. CONCLUSION. All formulations were safe and well tolerated in a malaria-endemic area of Africa in healthy adults. The ProC6CAlOH/Matrix-M vaccine elicited the highest levels of functional antibodies, meriting further investigation.

Original language	English
Article number	e175707
Journal	Journal of Clinical Investigation
Volume	134
Issue number	7
DOIs	https://doi.org/10.1172/JCI175707
Publication status	Published - 1 Apr 2024
Externally published	Yes

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Tiono, A. B., Plieskatt, J. L., Ouedraogo, A., Soulama, B. I., Miura, K., Bougouma, E. C., Naghizadeh, M., Barry, A., Yaro, J. B. B., Ezinmegnon, S., Henry, N., Ofori, E. A., Adu, B., Singh, S. K., Konkobo, A., Bengtsson, K. L., Diarra, A., Carnrot, C., Reimer, J. M., ... Theisen, M. (2024). A randomized first-in-human phase I trial of differentially adjuvanted Pfs48/45 malaria vaccines in Burkinabé adults. Journal of Clinical Investigation, 134(7), Article e175707. https://doi.org/10.1172/JCI175707

@article{e1ca2973372b4e61bc65472192ed45e5,

title = "A randomized first-in-human phase I trial of differentially adjuvanted Pfs48/45 malaria vaccines in Burkinab{\'e} adults",

abstract = "BACKGROUND. Malaria transmission-blocking vaccines aim to interrupt the transmission of malaria from one person to another. METHODS. The candidates R0.6C and ProC6C share the 6C domain of the Plasmodium falciparum sexual-stage antigen Pfs48/45. R0.6C utilizes the glutamate-rich protein (GLURP) as a carrier, and ProC6C includes a second domain (Pfs230-Pro) and a short 36–amino acid circumsporozoite protein (CSP) sequence. Healthy adults (n = 125) from a malaria-endemic area of Burkina Faso were immunized with 3 intramuscular injections, 4 weeks apart, of 30 μg or 100 μg R0.6C or ProC6C each adsorbed to Alhydrogel (AlOH) adjuvant alone or in combination with Matrix-M (15 μg or 50 μg, respectively). The allocation was random and double-blind for this phase I trial. RESULTS. The vaccines were safe and well tolerated with no vaccine-related serious adverse events. A total of 7 adverse events, mild to moderate in intensity and considered possibly related to the study vaccines, were recorded. Vaccine-specific antibodies were highest in volunteers immunized with 100 μg ProC6C-AlOH with Matrix-M, and 13 of 20 (65%) individuals in the group showed greater than 80% transmission-reducing activity (TRA) when evaluated in the standard membrane feeding assay at 15 mg/mL IgG. In contrast, R0.6C induced sporadic TRA. CONCLUSION. All formulations were safe and well tolerated in a malaria-endemic area of Africa in healthy adults. The ProC6CAlOH/Matrix-M vaccine elicited the highest levels of functional antibodies, meriting further investigation.",

author = "Tiono, {Alfred B.} and Plieskatt, {Jordan L.} and Alphonse Ouedraogo and Soulama, {Ben Idriss} and Kazutoyo Miura and Bougouma, {Edith C.} and Mohammad Naghizadeh and Aissata Barry and Yaro, {Jean Baptist B.} and Sem Ezinmegnon and Noelie Henry and Ofori, {Ebenezer Addo} and Bright Adu and Singh, {Susheel K.} and Augustin Konkobo and Bengtsson, {Karin L{\"o}vgren} and Amidou Diarra and Cecilia Carnrot and Reimer, {Jenny M.} and Amidou Ouedraogo and Moussa Tienta and Long, {Carole A.} and Ouedraogo, {Issa N.} and Issaka Sagara and Sirima, {Sodiomon B.} and Michael Theisen",

note = "Publisher Copyright: {\textcopyright} 2024, Tiono et al.",

year = "2024",

month = apr,

day = "1",

doi = "10.1172/JCI175707",

language = "English",

volume = "134",

journal = "Journal of Clinical Investigation",

issn = "0021-9738",

publisher = "American Society for Clinical Investigation",

number = "7",

}

Tiono, AB, Plieskatt, JL, Ouedraogo, A, Soulama, BI, Miura, K, Bougouma, EC, Naghizadeh, M, Barry, A, Yaro, JBB, Ezinmegnon, S, Henry, N, Ofori, EA, Adu, B, Singh, SK, Konkobo, A, Bengtsson, KL, Diarra, A, Carnrot, C, Reimer, JM, Ouedraogo, A, Tienta, M, Long, CA, Ouedraogo, IN, Sagara, I, Sirima, SB & Theisen, M 2024, 'A randomized first-in-human phase I trial of differentially adjuvanted Pfs48/45 malaria vaccines in Burkinabé adults', Journal of Clinical Investigation, vol. 134, no. 7, e175707. https://doi.org/10.1172/JCI175707

TY - JOUR

T1 - A randomized first-in-human phase I trial of differentially adjuvanted Pfs48/45 malaria vaccines in Burkinabé adults

AU - Tiono, Alfred B.

AU - Plieskatt, Jordan L.

AU - Ouedraogo, Alphonse

AU - Soulama, Ben Idriss

AU - Miura, Kazutoyo

AU - Bougouma, Edith C.

AU - Naghizadeh, Mohammad

AU - Barry, Aissata

AU - Yaro, Jean Baptist B.

AU - Ezinmegnon, Sem

AU - Henry, Noelie

AU - Ofori, Ebenezer Addo

AU - Adu, Bright

AU - Singh, Susheel K.

AU - Konkobo, Augustin

AU - Bengtsson, Karin Lövgren

AU - Diarra, Amidou

AU - Carnrot, Cecilia

AU - Reimer, Jenny M.

AU - Ouedraogo, Amidou

AU - Tienta, Moussa

AU - Long, Carole A.

AU - Ouedraogo, Issa N.

AU - Sagara, Issaka

AU - Sirima, Sodiomon B.

AU - Theisen, Michael

PY - 2024/4/1

Y1 - 2024/4/1

N2 - BACKGROUND. Malaria transmission-blocking vaccines aim to interrupt the transmission of malaria from one person to another. METHODS. The candidates R0.6C and ProC6C share the 6C domain of the Plasmodium falciparum sexual-stage antigen Pfs48/45. R0.6C utilizes the glutamate-rich protein (GLURP) as a carrier, and ProC6C includes a second domain (Pfs230-Pro) and a short 36–amino acid circumsporozoite protein (CSP) sequence. Healthy adults (n = 125) from a malaria-endemic area of Burkina Faso were immunized with 3 intramuscular injections, 4 weeks apart, of 30 μg or 100 μg R0.6C or ProC6C each adsorbed to Alhydrogel (AlOH) adjuvant alone or in combination with Matrix-M (15 μg or 50 μg, respectively). The allocation was random and double-blind for this phase I trial. RESULTS. The vaccines were safe and well tolerated with no vaccine-related serious adverse events. A total of 7 adverse events, mild to moderate in intensity and considered possibly related to the study vaccines, were recorded. Vaccine-specific antibodies were highest in volunteers immunized with 100 μg ProC6C-AlOH with Matrix-M, and 13 of 20 (65%) individuals in the group showed greater than 80% transmission-reducing activity (TRA) when evaluated in the standard membrane feeding assay at 15 mg/mL IgG. In contrast, R0.6C induced sporadic TRA. CONCLUSION. All formulations were safe and well tolerated in a malaria-endemic area of Africa in healthy adults. The ProC6CAlOH/Matrix-M vaccine elicited the highest levels of functional antibodies, meriting further investigation.

AB - BACKGROUND. Malaria transmission-blocking vaccines aim to interrupt the transmission of malaria from one person to another. METHODS. The candidates R0.6C and ProC6C share the 6C domain of the Plasmodium falciparum sexual-stage antigen Pfs48/45. R0.6C utilizes the glutamate-rich protein (GLURP) as a carrier, and ProC6C includes a second domain (Pfs230-Pro) and a short 36–amino acid circumsporozoite protein (CSP) sequence. Healthy adults (n = 125) from a malaria-endemic area of Burkina Faso were immunized with 3 intramuscular injections, 4 weeks apart, of 30 μg or 100 μg R0.6C or ProC6C each adsorbed to Alhydrogel (AlOH) adjuvant alone or in combination with Matrix-M (15 μg or 50 μg, respectively). The allocation was random and double-blind for this phase I trial. RESULTS. The vaccines were safe and well tolerated with no vaccine-related serious adverse events. A total of 7 adverse events, mild to moderate in intensity and considered possibly related to the study vaccines, were recorded. Vaccine-specific antibodies were highest in volunteers immunized with 100 μg ProC6C-AlOH with Matrix-M, and 13 of 20 (65%) individuals in the group showed greater than 80% transmission-reducing activity (TRA) when evaluated in the standard membrane feeding assay at 15 mg/mL IgG. In contrast, R0.6C induced sporadic TRA. CONCLUSION. All formulations were safe and well tolerated in a malaria-endemic area of Africa in healthy adults. The ProC6CAlOH/Matrix-M vaccine elicited the highest levels of functional antibodies, meriting further investigation.

UR - http://www.scopus.com/inward/record.url?scp=85189299060&partnerID=8YFLogxK

U2 - 10.1172/JCI175707

DO - 10.1172/JCI175707

M3 - Article

C2 - 38290009

AN - SCOPUS:85189299060

SN - 0021-9738

VL - 134

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

IS - 7

M1 - e175707

ER -

A randomized first-in-human phase I trial of differentially adjuvanted Pfs48/45 malaria vaccines in Burkinabé adults

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