Malaria is a major public health problem. There were around 240 million cases of malariaand 627,000 deaths worldwide in 2020. Most of the deaths are in children under fiveliving in Africa. It is a major problem for those who live in affected areas and fortravellers. There is a great need for a safe, effective malaria vaccine.This study is being done to evaluate an experimental malaria vaccine for its safety andalso look at the body's immune response to the vaccine.The vaccine tested in this study is called and "RH5.1". This is given with an adjuvantcalled "Matrix-M". This is a substance to improve the body's response to a vaccination.The aim is to use the vaccines and adjuvant to help the body make an immune responseagainst parts of the malaria parasite. This study will assess: 1. The safety of the vaccines in healthy participants. 2. The response of the human immune system to the vaccines.This will be achieved by giving participants three doses of the RH5.1 vaccines at twodifferent dose levels (10 micrograms and 50 micrograms). One group will have 3 doses of10 micrograms given at 0, 1 and 6 months whilst the other will receive 2 doses of 50micrograms (at 1 and 2 months) followed by a 10 microgram dose at 6 months- known as a'delayed fractional dose'. Blood tests and information about any symptoms will beperformed/collected that occur after vaccination.Information from previous studies suggests that a delayed fractional dose improves theimmune response to the vaccine, particularly in terms of the antibody response. Currentprediction is that this improvement is due to the delay in dosing, rather than thereduction in dose, and this study will help to answer that. Having a vaccine at a singledose is important for efficient production and dosing for vaccines rolled out in nationalprograms so being able to move away from 'delayed fractional dose' regimens to 'delayedfinal dose' regimens will be important for vaccine development.
Not Provided
Biological: Matrix M with RH5.1
50 µg of Matrix-M adjuvant with RH5.1 at different doses on days 0 and 28.
Inclusion Criteria:
- Healthy adult aged 18 to 50 years
- Able and willing (in the Investigator's opinion) to comply with all study
requirements.
- Willing to allow the Investigators to discuss the volunteer's medical history with
their GP
- Participants of childbearing potential only: must practice continuous effective
contraception for the duration of the study (see section 9.9)
- 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) or previous participation in any malaria
(vaccine) trial or controlled human malaria infection (CHMI) study
- Travel to a clearly malaria endemic locality during the study period or within the
preceding six months
- Use of immunoglobulins or blood products (e.g. blood transfusion) in the last three
months
- Receipt of any vaccine in the 30 days preceding enrolment, or planned receipt of any
other vaccine within 30 days following each study vaccination, with the exception of
COVID-19 vaccines, which should not be received between 14 days before to 7 days
after any study vaccination
- Receipt of an investigational product in the 30 days preceding enrolment, or planned
receipt during the study period
- Concurrent involvement in another clinical trial involving an investigational
product or planned involvement during the study period
- Prior receipt of an investigational vaccine likely to impact on interpretation of
the trial data, as assessed by the Investigator
- Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV
infection; asplenia; recurrent, severe infections and chronic (more than 14 days)
immunosuppressant medication within the past 6 months (inhaled and topical steroids
are allowed)
- History of allergic disease or reactions likely to be exacerbated by any component
of the vaccine
- Any history of anaphylaxis
- Pregnancy, lactation or intention to become pregnant during the study
- Body mass index of <18.5 or >35
- History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in
situ)
- 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 misuse as defined by an alcohol intake of greater
than 25 standard UK units every week
- Suspected or known injecting drug use in the 5 years preceding enrolment
- Hepatitis B surface antigen (HBsAg) detected in serum
- Seropositive for hepatitis C virus (antibodies to HCV) at screening (unless
volunteer has taken part in a prior hepatitis C vaccine study with confirmed
negative HCV antibodies prior to participation in that study, and negative HCV
ribonucleic acid (RNA) PCR at screening for this study)
- Volunteers unable to be closely followed for social, geographic or psychological
reasons.
- Any clinically significant abnormal finding on biochemistry or haematology blood
tests, urinalysis or clinical examination. Blood test abnormalities will be assessed
as per the laboratory adverse event table in Appendix A (table 8). In the event of
abnormal test results deemed to be clinically significant, confirmatory repeat tests
may be requested. Procedures for identifying laboratory values meeting exclusion
criteria are described in Appendix A.
- Any other significant disease, disorder, or finding which may significantly increase
the risk to the volunteer because of participation in the study, affect the ability
of the volunteer to participate in the study or impair interpretation of the study
data
- Inability of the study team to contact the volunteer's GP to confirm medical history
and safety to participate
Sheffield Teaching Hospitals, Royal Hallamshire Hospital
Sheffield, United Kingdom
Not Provided