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

Research output: Contribution to journalJournal articleResearchpeer-review


  • Alfred B Tiono
  • Jordan L Plieskatt
  • Alphonse Ouedraogo
  • Ben Idriss Soulama
  • Kazutoyo Miura
  • Edith C Bougouma
  • Aissata Barry
  • Jean Baptist B Yaro
  • Sem Ezinmegnon
  • Noelie Henry
  • 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

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).

Original languageEnglish
Article numbere175707
JournalThe Journal of Clinical Investigation
Issue number7
Number of pages15
Publication statusPublished - 2024

ID: 387149322