Controlled Human Infection for Vaccination Against Streptococcus Pyogenes

Inclusion Criteria: * Males or females, aged 18 - 40 years (inclusive) on the day of informed consent. * Medically healthy, determined by medical history, physical examination, transthoracic echocardiogram, non-clinically significant laboratory profiles, vital signs, and 12-lead ECG at screening, as deemed by the investigator. * No active or chronic diseases/disorders, no history of hospitalisation for illness within the six months prior to enrolment into study, and no major surgery within the 12 months prior to enrolment into study. * Body mass index of 18.0 - 32.0 kg/m2 and body weight ≥ 50.0kg * Systolic blood pressure (SBP) of 90 mmHg - 140 mmHg and diastolic blood pressure (DBP) of 50 mmHg - 90 mmHg. Vital signs can be repeated up to two times. * Resting heart rate (HR), as measured by ECG of 40bpm - 100 bpm (confirmed by one repeat at screening). * Females must be non-pregnant, non-lactating or postmenopausal for at least 1 year (as confirmed by follicle-stimulating hormone \[FSH\]), or surgically sterile for at least 6 months prior to dosing. * All male and females of childbearing potential must agree to use two forms of acceptable contraception from the time of signing informed consent until 30 days after final dose of rifampicin. * Acceptable forms of contraception include: barrier method (eg. condom, diaphragm); pharmacological hormonal methods (oral contraceptive pill, long-acting implantable, intrauterine device). * Rifampicin may reduce the activity of oral and implantable contraceptives (not intrauterine devices) so additional use of a barrier method is required for 30 days after the final dose of rifampicin for participants using these methods. * Participants who abstain from penile-vaginal intercourse are eligible when this is their preferred and usual lifestyle. These participants must not be planning in vitro fertilization within the study and follow-up period. * Must be willing and able to read, understand, and sign the participant information and consent form. * Able and willing (in the Investigator's opinion) to comply with all study requirements, including the in-patient confinement period and outpatient visits for the duration of the study (approximately 6 months including follow-up visits). Exclusion Criteria: * History of any clinically important cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, and renal, or other major disease, as determined by the Investigator. * History of tonsillectomy, adenoidectomy or splenectomy. * Known or suspected autoimmune disease or impairment/alteration of immune function resulting from: * Congenital or acquired immunodeficiency (including immunoglobulin A deficiency) * Receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months. * Presence or history of a severe drug hypersensitivity, or allergic disease diagnosed and treated by a physician or history of a severe allergic reaction, anaphylaxis or convulsions following any vaccination or infusion. * Personal or family history of severe GAS infection or sequelae (such as acute rheumatic fever, rheumatic heart disease, post-streptococcal glomerulonephritis) or invasive GAS disease (toxic shock syndrome, necrotizing fasciitis, bloodstream infection, pleural empyema, meningitis). * Clinically significant disease or any condition or disease that might affect drug absorption, distribution or excretion, e.g. gastrectomy, diarrhea. * Any vaccination within the last 28 days or use of any antibiotic therapy during the 14 days before challenge. * Presence of acute infectious disease or febrile illness (e.g., sub-lingual temperature ≥ 38.5°C) within the five days prior to inoculation. * Significant acute or chronic infection within 14 days prior to inoculation that the Investigator deems may compromise participant safety. * Any clinically significant abnormal finding on biochemistry or haematology blood tests, urine analysis, ECG or transthoracic echocardiogram. * Positive serologic results for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg), and/or hepatitis C virus (HCV) antibodies. * Ex-smoker with a \>10 pack year smoking history or a current smoker who is unable to stop smoking for the duration of the study * History or presence of alcohol abuse (defined as regular alcohol consumption of more than 40g per day) or drug habituation, or any prior intravenous usage of an illicit substance. * A positive urine drug test at screening or admission for confinement (e.g., amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, and opiates) unless there is an explanation acceptable to the investigator or sub-investigator (e.g. the participant has stated in advance that they consumed a prescription or over-the-counter product which contained the detected drug) and the participant has a negative urine drug screen on retest. * A positive alcohol breath test at screening or admission for confinement. * Known hypersensitivity or other contraindication to use of penicillin, rifampicin or any other beta-lactam or rifamycin antibiotic(s). * Known hypersensitivity or contraindication to both azithromycin and clindamycin. * Known hypersensitivity to soya protein. * Intolerance of throat swab procedure (exaggerated gag reflex). * Any systemic corticosteroid (or equivalent) treatment in the 14 days prior to challenge, or for more than seven consecutive days within the past 3 months. * Any corticosteroids, anti-inflammatory drugs (besides sporadic use of non-steroidal anti-inflammatory drugs), immunomodulators or anticoagulants in the previous 3 months, or anticipated use of such drugs during the study period. Any participant currently receiving or having previously received immunosuppressive therapy, including systemic steroids including adrenocorticotrophic hormone (ACTH) or inhaled steroids in dosages which are associated with hypothalamic-pituitary-adrenal axis suppression such as 1 mg/kg/day of prednisone or its equivalent or chronic use of inhaled high potency corticosteroids (budesonide 800 μg or fluticasone 750 μg per day). Intranasal corticosteroid use is not allowed from 14 days prior to admission, during the confinement period, and is discouraged prior to the first outpatient visit. Topical corticosteroid use is allowed. * Use of prescription or non-prescription drugs and herbal supplements (such as St John´s Wort) within 14 days or 5 half-lives (whichever is the longer) prior to the inoculation administration. Use of vitamin supplements taken at standard doses is allowed. * Participation in a research study that involved blood sampling of more than 450 mL/unit of blood, received or donated blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation within 3 months of informed consent. * History of severe infectious disease requiring hospitalisation for intravenous antibiotics. * History of cancer (except adequately treated squamous cell or basal cell carcinoma of the skin and cervical intraepithelial neoplasia). * Presence of implants or prosthesis (e.g. artificial joints, pacemakers). * Participation in another research study within the 30 days prior to enrolment involving an investigational product or other intervention that might affect risk of invasive GAS infection or compromise the integrity of the study (e.g. significant volumes of blood already taken in previous study). * Any significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the study, or may influence the results of the study, or the participant's ability to participate in the study. * Any employee of the sponsor or research site personnel directly affiliated with this study or their immediate family members defined as a spouse, parent, sibling, or child whether biological or legally adopted. * Evidence of pre-existing immunity to the challenge strain as determined by quantitative +/- functional antibody testing of serum collected at the screening visit