1. A randomized first-in-human phase I trial of differentially adjuvanted Pfs48/45 malaria vaccines in Burkinabe adults
- Author
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Tiono, Alfred B., Plieskatt, Jordan L., Ouedraogo, Alphonse, Soulama, Ben Idriss, Miura, Kazutoyo, Bougouma, Edith C., Naghizadeh, Mohammad, Barry, Aissata, Yaro, Jean Baptist B., Ezinmegnon, Sem, Henry, Noelie, Ofori, Ebenezer Addo, Adu, Bright, Singh, Susheel K., Konkobo, Augustin, Bengtsson, Karin Lovgren, Diarra, Amidou, Carnrot, Cecilia, Reimer, Jenny M., Ouedraogo, Amidou, Tienta, Moussa, Long, Carole A., Ouedraogo, Issa N., Sagara, Issaka, Sirima, Sodiomon B., and Theisen, Michael
- Subjects
United States. National Institute of Allergy and Infectious Diseases ,Medical research ,Medicine, Experimental ,Malaria vaccine -- Product development ,Glutamate -- Product development ,Amino acids -- Product development ,Antigens ,Clinical trials ,Malaria ,Adults ,Vaccines -- Product development ,Immunoglobulin G ,Plasmodium falciparum ,Health care industry - 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 [micro]g or 100 [micro]g R0.6C or ProC6C each adsorbed to Alhydrogel (AlOH) adjuvant alone or in combination with Matrix-M (15 [micro]g or 50 [micro]g, 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 [micro]g 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)., Introduction Plasmodium falciparum malaria is transmitted by mosquitoes of the genus Anopheles. During a blood meal from an infected person, the female mosquito ingests sexual-stage parasites, which fertilize in the [...]
- Published
- 2024
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