A study of three malaria vaccines to prevent the transmission of malaria in adults in Mali: TBVax2

INTERVENTION: This is a study to assess the safety, tolerability, immunogenicity, and transmission‐blocking activity (TBA) of a 3 dose regimen of Study Agents (four total) versus rabies vaccine in healthy adults. This will be a first‐in‐human assessment of the co‐administration of R0.6C‐AlOH/Matrix‐M with Pfs230D1‐EPA/Matrix‐M. Participants will be randomized to one of the study arms. Participants will be followed for 12 months from the last dose of the study vaccine for safety and tolerability, as well as immunogenicity and functional antibody responses. 1. Group 1: Pilot Group 1.1. Arm 1a (n=5): 30 µg ProC6C‐AlOH/15 µg Matrix‐M (this arm is to be enrolled only if safety has not already been demonstrated in the ongoing first‐in‐human trial PACTR202201848463189) 1.2. Arm 1b (n=5): 30 µg R0.6C‐AlOH/15 µg Matrix‐M co‐administered with 12.5 µg Pfs230D1‐EPA/25 µg Matrix‐M 1.3. Arm 1c (n=5): rabies vaccine (standard dose) 2. Group 2: Main Group 2.1. Arm 2a (n=20): 100 µg R0.6C‐AlOH/50 µg Matrix‐M and normal saline 2.2. Arm 2b (n=20): 100 µg ProC6C‐AlOH/50 µg Matrix‐M and normal saline 2.3. Arm 2c (n=20): 40 µg Pfs230D1‐EPA/50 µg Matrix‐M and normal saline (Pfs230D1‐EPA regimen may be adjusted based on results of ongoing clinical trial NCT05135273) 2.4. Arm 2d (n=20): 100 µg R0.6C‐AlOH/25 µg Matrix‐M co‐administered with 40 µg Pfs230D1‐EPA/25 µg Matrix‐M (Pfs230D1‐EPA regimen may be adjusted based on ongoing clinical trial PACTR202201848463189) 2.5. Arm 2e (n=20): rabies vaccine (standard dose) CONDITION: Prevention of Plasmodium falciparum transmission in humans ; Infections and Infestations PRIMARY OUTCOME: 1. Incidence of serious adverse events (SAEs) possibly, probably or definitely related to co‐administered vaccinations, measured clinically and by laboratory assessments, measured 7 days after each vaccination in the period from first vaccinations up to 1 month after the last immunization: ; 1.1. That results in death; 1.2. That is life‐threatening (places the participant at immediate risk of death from the event as it occurred); 1.3. That requires inpatient hospitalization or prolongs an existing hospitalization; 2. Incidence of solicited grade 3 local and systemic adverse events (AEs) possibly, probably or definitely related to co‐administered vaccinations, measured clinically and by laboratory assessments, measured 7 days after each vaccination in the period from first vaccinations up to 1 month after the last immunization:; 2.1. Systemic adverse events: ; 2.1.1. Fever (temperature = 38.0°c); 2.1.3. Headache; 2.1.4. Nausea/vomiting; 2.1.5. Diarrhea; 2.1.6. Abdominal pain; 2.1.7. Fatigue; 2.1.8. Malaise; 2.1.9. Myalgia; 2.1.10. Arthralgia; 2.1.11. Urticarial; 2.2. Local reactogenicity following the injection:; 2.2.1 Pain/tenderness; 2.2.2. Erythema/redness; 2.2.3. Swelling; 2.2.3. Induration; 2.2.4. Pruritus; 2.2.5. Limitation of arm movement INCLUSION CRITERIA: 1. Aged between 18 years old and < 50 years old 2. Available for the duration of the trial 3. Known resident or long‐term resident (more than 1 year) of Doneguebougou or surrounding villages 4. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process 5. In good general health and without clinically significant medical history in the opinion of the investigator 6. Females of childbearing potential must be willing to use reliable contraception from 21 days prior to Study Day 0 and until 1 month after the last vaccination 7. Willing to have blood samples stored for future research SECONDARY OUTCOME: 1. The functional transmission reducing activity (TRA) measured using the standard membrane feeding assay of volunteer sera at two weeks after the third immunizations, compared to baseline within each of the Study Agent Groups; 2. The TRA measured using the standard membrane feeding assay of volunteer sera at other time points (2 weeks after first and second immunizations and 4 months post third vaccination) compared to baseline (D0) in each of the Study Agent Groups; 3. The Study Agent antibody quantity in volunteer sera measured by ELISA two weeks after each dose and at 4 months post dose compared to baseline (D0) in each of the three dose‐adjuvant combinations; 4. Incidence of adverse events possibly, probably or definitely related to any investigational vaccines measured clinically and by laboratory assessments at study duration period