A randomized first-in-human phase I trial of differentially adjuvanted Pfs48/45 malaria vaccines in Burkinabé adults
Alfred B. Tiono, … , Sodiomon B. Sirima, Michael Theisen
Alfred B. Tiono, … , Sodiomon B. Sirima, Michael Theisen
Published January 30, 2024
Citation Information: J Clin Invest. 2024;134(7):e175707. https://doi.org/10.1172/JCI175707.
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Clinical Research and Public Health Infectious disease

A randomized first-in-human phase I trial of differentially adjuvanted Pfs48/45 malaria vaccines in Burkinabé 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 ProC6C-AlOH/Matrix-M vaccine elicited the highest levels of functional antibodies, meriting further investigation.TRIAL REGISTRATION Pan-African Clinical Trials Registry (https://pactr.samrc.ac.za) PACTR202201848463189.FUNDING The study was funded by the European and Developing Countries Clinical Trials Partnership (grant RIA2018SV-2311).

Authors

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

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Figure 1

Study flow.

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Study flow. Overview of trial flow for cohort 1 (low dose) and cohort 2 ...
Overview of trial flow for cohort 1 (low dose) and cohort 2 (high-dose) first-in-human trial of R0.C6-AlOH/MM and ProC6C-AlOH/MM. A total of 207 participants were screened. A total of 9 individuals did not complete the study, of whom 2 individuals withdrew their consent (groups 2A, 2C) and received only 1 and 2 vaccinations, respectively. An additional 2 migrated out the study area (groups 1C, 2B), and 4 individuals were reported as lost to follow-up (groups 2A, 2C, 2E, 2E). One individual (group 2B) tested positive for pregnancy and did not receive the third vaccine dose but has been followed up to the end of the study for safety reasons.