Safety and Immunogenicity of Pfs25M-EPA/AS01 and Pfs230D1M-EPA/AS01 Vaccines, Transmission Blocking Vaccines Against Plasmodium Falciparum, at Full and Fractional Dosing in Adults in Mali

Summary

Background: Researchers are looking for new ways to control and eradicate malaria. They want to test vaccines to block malaria transmission in adults in Mali. These vaccines work by inducing antibodies in a person. The antibody is then taken up with blood by a mosquito that bites the person. This blocks parasite development in the mosquito. This stops malaria transmission to another person. Objective: To test the safety, reactogenicity, immunogenicity, and transmission-blocking activity of the vaccines Pfs25M-EPA and Pfs230D1M-EPA with AS01 in Malian adults. Eligibility: Healthy Malians ages 18-50 living in certain areas in Mali who: Are not pregnant or breastfeeding Are not infected with HIV, Hepatitis B and Hepatitis C Do not have evidence of immunodeficiency Do not have history of severe allergic reaction or anaphylaxis Design: Participants will be screened with: Medical history Physical exam Malaria Comprehension Exam Blood and urine tests Electrocardiogram (for participants in certain study groups) Participants will be randomly assigned to a study group. Participants will be monitored for 12-16 months. For the first 7 months, they will have between 1 and nine visits a month. The number depends on the month and on what group they are in. For the rest of the months, they will have 1 monthly visit. Each visit includes a physical exam. Most include blood tests. Participants will get 3 doses of a study or comparator vaccine. They get the vaccine through an injection in the upper arm. This occurs at their first visit, then 1 month later, and then 5 months later. Participants will be followed for at least 6 months after the last vaccine. If participants develop an injection site rash or reaction, photographs may be taken of the site.

Timeline

Start

2016-10-21

Primary completion

2020-07-15

Completion

2020-07-15

Publications

• Background Wu Y, Przysiecki C, Flanagan E, Bello-Irizarry SN, Ionescu R, Muratova O, Dobrescu G, Lambert L, Keister D, Rippeon Y, Long CA, Shi L, Caulfield M, Shaw A, Saul A, Shiver J, Miller LH. Sustained high-titer antibody responses induced by conjugating a malarial vaccine candidate to outer-membrane protein complex. Proc Natl Acad Sci U S A. 2006 Nov 28;103(48):18243-8. doi: 10.1073/pnas.0608545103. Epub 2006 Nov 16.
• Background Tachibana M, Wu Y, Iriko H, Muratova O, MacDonald NJ, Sattabongkot J, Takeo S, Otsuki H, Torii M, Tsuboi T. N-terminal prodomain of Pfs230 synthesized using a cell-free system is sufficient to induce complement-dependent malaria transmission-blocking activity. Clin Vaccine Immunol. 2011 Aug;18(8):1343-50. doi: 10.1128/CVI.05104-11. Epub 2011 Jun 29.
• Background Diallo M, Toure AM, Traore SF, Niare O, Kassambara L, Konare A, Coulibaly M, Bagayogo M, Beier JC, Sakai RK, Toure YT, Doumbo OK. Evaluation and optimization of membrane feeding compared to direct feeding as an assay for infectivity. Malar J. 2008 Dec 2;7:248. doi: 10.1186/1475-2875-7-248.
• Healy SA, Sagara I, Assadou MH, Katile A, Kone M, Imeru A, Kwan JL, Swihart BJ, Fintzi J, Potter GE, Zeguime A, Dolo A, Diarra B, Narum DL, Rausch KM, MacDonald NJ, Zhu D, Mohan R, Thera I, Morrison RD, Zaidi I, Doritchamou JYA, Sylla D, Hume JCC, Coulibaly MB, Morelle D, Lievens M, Doumbo OK, Duffy PE; Pfs230D1 Vaccine Team. A Vaccine to Block Plasmodium falciparum Transmission. NEJM Evid. 2025 Jul;4(7):EVIDoa2400188. doi: 10.1056/EVIDoa2400188. Epub 2025 Jun 24.
• Cao Y, da Silva Araujo M, Lorang CG, Dos Santos NAC, Tripathi A, Vinetz J, Kumar N. Distinct immunogenicity outcomes of DNA vaccines encoding malaria transmission-blocking vaccine target antigens Pfs230D1M and Pvs230D1. Vaccine. 2025 Feb 15;47:126696. doi: 10.1016/j.vaccine.2024.126696. Epub 2025 Jan 8.

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