A randomized first-in-human phase I trial of differentially adjuvanted Pfs48/45 malaria vaccines in Burkinabé adults
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A randomized first-in-human phase I trial of differentially adjuvanted Pfs48/45 malaria vaccines in Burkinabé adults. / Tiono, Alfred B; Plieskatt, Jordan L; Ouedraogo, Alphonse; Soulama, Ben Idriss; Miura, Kazutoyo; Bougouma, Edith C; Naghizadeh, Mohammad; Barry, Aissata; Yaro, Jean Baptist B; Ezinmegnon, Sem; Henry, Noelie; Ofori, Ebenezer Addo; Adu, Bright; Singh, Susheel K; Konkobo, Augustin; Lövgren Bengtsson, Karin; Diarra, Amidou; Carnrot, Cecilia; Reimer, Jenny M; Ouedraogo, Amidou; Tienta, Moussa; Long, Carole A; Ouedraogo, Issa N; Sagara, Issaka; Sirima, Sodiomon B; Theisen, Michael.
In: The Journal of Clinical Investigation, Vol. 134, No. 7, e175707, 2024.Research output: Contribution to journal › Journal article › Research › peer-review
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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 - Lövgren Bengtsson, Karin
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
Y1 - 2024
N2 - BACKGROUNDMalaria transmission-blocking vaccines aim to interrupt the transmission of malaria from one person to another.METHODSThe 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.RESULTSThe 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.CONCLUSIONAll formulations were safe and well tolerated in a malaria-endemic area of Africa in healthy adults. The ProC6C-AlOH/Matrix-M vaccine elicited the highest levels of functional antibodies, meriting further investigation.TRIAL REGISTRATIONPan-African Clinical Trials Registry (https://pactr.samrc.ac.za) PACTR202201848463189.FUNDINGThe study was funded by the European and Developing Countries Clinical Trials Partnership (grant RIA2018SV-2311).
AB - BACKGROUNDMalaria transmission-blocking vaccines aim to interrupt the transmission of malaria from one person to another.METHODSThe 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.RESULTSThe 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.CONCLUSIONAll formulations were safe and well tolerated in a malaria-endemic area of Africa in healthy adults. The ProC6C-AlOH/Matrix-M vaccine elicited the highest levels of functional antibodies, meriting further investigation.TRIAL REGISTRATIONPan-African Clinical Trials Registry (https://pactr.samrc.ac.za) PACTR202201848463189.FUNDINGThe study was funded by the European and Developing Countries Clinical Trials Partnership (grant RIA2018SV-2311).
U2 - 10.1172/JCI175707
DO - 10.1172/JCI175707
M3 - Journal article
C2 - 38290009
VL - 134
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 7
M1 - e175707
ER -
ID: 387149322