Portal de Periódicos da CAPES

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

2024; American Society for Clinical Investigation; Volume: 134; Issue: 7 Linguagem: Inglês

10.1172/jci175707

1558-8238

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

Complement system in diseases

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).