| Title: |
A randomized first-in-human phase I trial of differentially adjuvanted Pfs48/45 malaria vaccines in Burkinabé adults |
| 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 |
| Source: |
The Journal of Clinical Investigation, Vol 134, Iss 7 (2024) |
| Publisher Information: |
American Society for Clinical Investigation |
| Publication Year: |
2024 |
| Collection: |
Directory of Open Access Journals: DOAJ Articles |
| Subject Terms: |
Infectious disease; Vaccines; Medicine |
| Description: |
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). |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://doi.org/10.1172/JCI175707; https://doaj.org/toc/1558-8238; https://doaj.org/article/3931addef9114faa99bd2bbf5347383b |
| Availability: |
https://doaj.org/article/3931addef9114faa99bd2bbf5347383b |
| Accession Number: |
edsbas.550FEFA3 |
| Database: |
BASE |