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
N1 - Publisher Copyright:
© 2024, Tiono et al.
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 - https://www.scopus.com/pages/publications/85189299060
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 -
