Safety, Immunogenicity and Efficacy of GSK S. Aureus Candidate Vaccine (GSK3878858A) When Administered to Healthy Adults (Dose-escalation) and to Adults 18 to 64 Years of Age With a Recent S. Aureus Skin and Soft Tissue Infection (SSTI)

Inclusion Criteria

All participants must satisfy all the following criteria at study entry:

• Participants who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visits).
• Written or witnessed informed consent obtained from the participant prior to performance of any study specific procedure.
• Participant satisfying screening requirements.
• Participants who, after the nature of the study has been explained to them, have shown adequate comprehension of the study procedures and knowledge of study.
• A male or female
• Dose escalation and safety lead-in phase: Aged between 18 and 50 years of age, inclusive, at the time of first vaccination.
• PoP phase: Aged between 18 and 64 years of age, inclusive, at the time of first vaccination.
• Female participants of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current bilateral tubal ligation or occlusion, hysterectomy, bilateral ovariectomy or post-menopause.
• Female participants of childbearing potential may be enrolled in the study, if the participant:
• has practiced adequate contraception for 30 days prior to vaccination,
• has a negative pregnancy test on the day of enrolment, and
• has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series.

Additional inclusion criteria only for participants to be enrolled in the dose-escalation safety lead-in screening epoch:

• Healthy participants as established by medical history, clinical examination and laboratory assessment.

Additional inclusion criteria only for participants to be enrolled in the PoP screening epoch:

• Healthy participants as established by medical history and clinical examination before entering into the study with an ongoing SSTI suspected to be caused by S. aureus, as diagnosed by investigator (before randomization participants have to be treated until clinical resolution of culture confirmed SSTI caused by S. aureus). SSTI must be amenable to microbiological culturing per standard clinical practice (i.e. recovery of drainage sample from abscess or suppurative cellulitis).

OR

• Healthy participants as established by medical history and clinical examination before entering into the study with an ongoing S. aureus SSTI (i.e. S. aureus is the most likely cause), as confirmed by a S. aureus positive culture performed outside the study procedures and not earlier than 30 days prior to Informed Consent Form signature. Before randomisation participants have to be treated until clinical resolution of the culture confirmed SSTI caused by S. aureus. These participants will be enrolled whether they have or have not already started specific treatment of the infection. In case they have not started the treatment, this will be then given in compliance with the standard medical practice for the management of S. aureus SSTIs and the choice and judgment of the most appropriate treatment will be applied by the investigator, outside the study procedures.

Exclusion Criteria

All participants at study entry

• Body mass index (BMI) >40 kg/m2
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine
• Hypersensitivity to latex
• Recurrent history of uncontrolled neurological disorders or seizures
• History of potential immune-mediated disease (pIMD)
• Clinical conditions that in the investigator's opinion represent a contraindication to intramuscular vaccination and blood draws
• Known bleeding diathesis or any condition that may be associated with a prolonged bleeding time
• Use of any investigational or non-registered product (drug, vaccine or medical device) other than the study vaccine(s) within 30 days before the first dose of study vaccine(s)/placebo (Day -29 to Day 1), or during the study period
• Chronic administration (defined as