This is a Phase Ib/II, open-label, head-to-head, age de-escalation dose-escalation, partially randomized trial to study the safety and immunogenicity of the candidate rabies vaccine ChAdOx2 RabG in healthy adults (age 18-45 years) and young children (age 2-6 years). ChAdOx2 RabG will be administered intramuscularly and licensed rabies vaccine will be given by intradermal injection.

A total of 120 participants will be recruited into 10 groups in Bagamoyo, Tanzania. The duration of the entire study will be up to 5.5 years per participant from the time of first vaccination. ChAdOx2 RabG will be administered intramuscularly and licensed rabies vaccine (Verorab) will be given by intradermal injection at two to four anatomical sites (deltoids, thighs or suprascapular areas).

All participants, regardless of which vaccine they receive at the start of the study, will receive a course of a licenced rabies vaccine (Verorab) during or at the end of the follow-up period.

Inclusion Criteria:

• Adult groups: Healthy male or female adults aged 18-45 years at the time of enrolment with signed consent.
• Adult groups (Female only participants): Must be non-pregnant (as demonstrated by a negative urine pregnancy test) and willing to use an effective form of contraception. Or if they agree to an extended period of follow-up of up to 5.5 years, use an effective form of contraception during the first year of enrolment in the study).
• Paediatric groups: Healthy male or female young children aged 2-6 years at the time of enrolment with signed consent obtained from parents or guardians.
• Paediatric groups: completion of the Expanded Programme on Immunisation (EPI) at least 6 months prior to study enrolment.
• Planned long-term (at least 61 months from the date of the first vaccination) or permanent residence in Bagamoyo town.
• Adults with a Body Mass Index (BMI) 18 to 35 Kg/m2; or young children with Z-score of weight-for-age within ±2SD.
• Correctly answer all 10 questions on the protocol and study procedures understanding questionnaire within 2 attempts.

Exclusion Criteria:

• Clinically significant congenital abnormalities as judged by the PI or other delegated individual.
• Clinically significant history of skin disorder, allergy, cardiovascular disease, respiratory disease, endocrine disorder, liver disease, renal disease, gastrointestinal disease and neurological illness 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 as judged by the PI or other delegated individual.
• 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).
• Any condition which would place the individual at elevated risk of serious COVID-19 infection, or any other factor which may make the individual eligible for priority COVID-19 vaccination (i.e. ahead of others in their age group).
• History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ).
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccines, including IRVs e.g. amphotericin B, chlortetracycline, neomycin, polymyxin, streptomycin
• Any history of anaphylaxis in relation to vaccination.
• Clinically significant laboratory abnormality as judged by the PI or other delegated individual.
• Receipt of any previous rabies vaccinations, including an incomplete course.
• History of vaccination with previous adenoviral vectored vaccines in the 6 months prior to enrolment in the study, or of vaccination with any other vaccine (including non-adenovirus-vectored COVID-19 vaccines) in the 28 days prior to enrolment.
• Planned / likely receipt of any other vaccine within 28 days after enrolment.
• History of bleeding disorder (e.g., factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture, or continuous anticoagulation e.g., with warfarin
• History of confirmed major thrombotic event, (including cerebral venous sinus thrombosis, deep vein thrombosis, pulmonary embolism) or,
• History of antiphospholipid syndrome.
• History of prior receipt of unfractionated heparin
• History of heparin induced thrombocytopenia
• Receipt of any blood products/ immunoglobulins within the three months preceding the planned administration of the vaccine candidate.
• Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period.
• Seropositive for hepatitis B surface antigen (HBsAg) or hepatitis C (HCV IgG).
• Likelihood of travel away from the study area.
• Female participant who is pregnant, lactating or planning pregnancy during the course of the trial.
• Scheduled elective surgery or other procedures requiring general anaesthesia during the trial.
• Any other significant disease, disorder or situation which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial.
• Contraindication to use of paracetamol

Deidentified participant data will be made available on direct request to the Principal Investigator. Proposals will be reviewed by the sponsor, Principal Investigator, and collaborators on the basis of scientific merit. Data will be shared following approval of the proposal and signed data-access agreements.