A Study of the Plasmodium Falciparum Malaria Vaccine Candidate Pfs48/45 in Matrix-M Adjuvant in the UK

Inclusion Criteria:

• Healthy adult aged 18 to 45 years.

• Able and willing (in the Investigator's opinion) to comply with all studyrequirements.

• Willing to allow the Investigators to discuss the volunteer's medical history withtheir GP.

• Volunteers with the potential to become pregnant only: must practice continuouseffective contraception for the duration of the study (see section 10.10).

• Agreement to refrain from blood donation for the duration of the study.

• Able and willing to provide written informed consent to participate in the trial

Exclusion Criteria:

• History of clinical malaria (any species).

• Travel to a clearly malaria endemic locality during the study period or within thepreceding six months.

• Use of immunoglobulins or blood products (e.g., blood transfusion) in the last threemonths.

• Receipt of any vaccine in the 30 days preceding enrolment, or planned receipt of anyother vaccine within 30 days following each study vaccination, with the exception ofCOVID-19 vaccines, which should not be received between 14 days before to 7 daysafter any study vaccination.

• Receipt of an investigational product in the 30 days preceding enrolment, or plannedreceipt during the study period.

• Concurrent involvement in another clinical trial or planned involvement during thestudy period.

• Prior receipt of an investigational vaccine likely to impact on interpretation ofthe trial data, as assessed by the Investigator.

• Any confirmed or suspected immunosuppressive or immunodeficient state, including HIVinfection; asplenia; recurrent, severe infections and chronic (more than 14 days)immunosuppressant medication within the past 6 months (inhaled and topical steroidsare allowed).

• History of allergic disease or reactions likely to be exacerbated by any componentof the vaccine.

• Any history of anaphylaxis in reaction to vaccinations.

• Pregnancy, lactation or intention to become pregnant during the study.

• History of cancer (except basal cell carcinoma of the skin and cervical carcinoma insitu).

• History of serious psychiatric condition that may affect participation in the study.

• Any other serious chronic illness requiring hospital specialist supervision.

• Suspected or known current alcohol abuse as defined by an alcohol intake of greaterthan 25 standard UK units every week.

• Suspected or known injecting drug abuse in the 5 years preceding enrolment.

• Hepatitis B surface antigen (HBsAg) detected in serum.

• Seropositive for hepatitis C virus (antibodies to HCV) at screening (unlessvolunteer has taken part in a prior hepatitis C vaccine study with confirmednegative HCV antibodies prior to participation in that study, and negative HCVribonucleic acid (RNA) PCR at screening for this study).

• Volunteers unable to be closely followed for social, geographic or psychologicalreasons.

• Any clinically significant abnormal finding on biochemistry or haematology bloodtests, urinalysis or clinical examination. In the event of abnormal test results,confirmatory repeat tests will be requested. Procedures for identifying laboratoryvalues meeting exclusion criteria are shown in SOP VC027.

• Any other significant disease, disorder, or finding which may significantly increasethe risk to the volunteer because of participation in the study, affect the abilityof the volunteer to participate in the study or impair interpretation of the studydata.

• Inability of the study team to contact the volunteer's GP to confirm medicalhistory.

Absolute contraindications:

• Anaphylactic reaction following administration of vaccine.

• Pregnancy.

Contraindications at that point in time (may be rescheduled):

• Acute disease at the time of vaccination. (Acute disease is defined as the presenceof a moderate or severe illness with or without fever). All vaccines can beadministered to persons with a minor illness such as diarrhoea, mild upperrespiratory infection with or without low-grade febrile illness, i.e. temperature of ≤37.5°C/99.5°F.

• Temperature of >37.5°C (99.5°F) at the time of vaccination.

• Current COVID-19 infection, defined as ongoing symptoms with positive COVID-19 PCRswab test taken during current illness or positive COVID-19 PCR swab or rapidantigen test within preceding 7 days without symptoms. Vaccinations will be delayedby a minimum of 7 days from the date of the first positive COVID-19 PCR swab orrapid antigen test, as long as symptoms are improving or resolved. It will be at thediscretion of the Investigator to withdraw a participant if they develop severeCOVID-19 disease.