This is a single blind randomised controlled trial (Phase 3 trial). This study aims to assess whether a half-dose of the R21/Matrix-M malaria vaccine is as effective as the full dose in children and adults. The results will help optimize vaccine usage and improve malaria prevention strategies.

All participants will receive the same number of injections and will be randomly assigned to receive one of the followings:

• Group 1: Adults and adolescents receiving the standard adult vaccine dose: 10μg R21/50μg Matrix-M (n=125).
• Group 2: Adults and adolescents receiving a half of the standard adult vaccine dose: 5μg R21/50μg Matrix-M: 10 dose vials with adaptor Preservative Free (n=125)
• Group 3: Adults and adolescents receiving a half of the standard adult vaccine dose: 5μg R21/50μg Matrix-M: 10 dose vials with 2PE Preservative (n=125)

Clinical procedure for participants:

• Standardized symptom questionnaire
• Physical examination:

Weight, height, pulse, blood pressure, respiratory rate, tympanic temperature. Spleen and liver size will be recorded if palpable. Pregnancy test (for female of child bearing potential)

• Venous blood collection (Pre-vaccination) 3mL
• Vaccination

This study was funded by Hanako Foundation. The grant reference number: 001/2026.

Inclusion Criteria:

• Residence in a study village for the study period, i.e. 12 months.
• Age 14 years to 60 years.
• Written informed consent/assent provided by participants (or a parent/guardian in case the participant is under 18 years old).

Exclusion Criteria:

• Pregnancy, plan to get pregnant within one month of vaccination, or breastfeeding.
• Acute illness requiring intervention.
• A history of an adverse reaction to study vaccine.
• Prior receipt of any other malaria vaccine.
• Enrolment in another intervention trial in the last month.
• Planned enrolment in another intervention trial in the coming 12 months.
• Regular use of Immunomodulating drugs e.g, Steroid, Methotrexate, Immunotherapy etc. in the past month and/or planned for the coming 12 months.

With participant's consent, participant's data and results from blood analyses stored in the database may be shared according to the terms defined in the MORU data sharing policy (https://www.tropmedres.ac/units/moru-bangkok/bioethics-engagement/data-sharing/moru-tropical-network-policy-on-sharing-data-and-other-outputs)with data repositories such as the WorldWide Antimalarial Resistance Network (WWARN, terms of submission here: http://www.wwarn.org/tools-resources/terms-submission) or other researchers to use in the future. All personal information will be anonymised so that no individual can be identified from their treatment records, through interviews, or from mapping data.