A Study to Evaluate Safety, Reactogenicity, and Immune Response of GVGH iNTS-TCV Vaccine Against Invasive Nontyphoidal Salmonella and Typhoid Fever

Inclusion criteria

• Participants, who, in the opinion of the Investigator, can and will comply with the requirements of the protocol.
• Written or witnessed/thumb printed informed consent obtained from the participant prior to performance of any study-specific procedure.
• Healthy participants as established by medical history, clinical examination, and laboratory assessment.
• Participant satisfying screening requirements.
• A male or female between and including 18 and 50 years of age at the time of the first study intervention administration.
• Female participants of nonchildbearing potential may be enrolled in the study. Nonchildbearing 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 trial if the participant:
• Has practiced adequate contraception for 1 month prior to study intervention administration, and
• Has a negative pregnancy test on the day of study intervention administration, and
• Has agreed to continue adequate contraception during the entire treatment period and for 1 month after completion of the study intervention administration series.
• Blood sample for simultaneous follicle-stimulating hormone (FSH) and estradiol levels may be collected at the discretion of the Investigator to confirm non-reproductive potential according to local laboratory reference range.
• Genetic testing for HLA-B27 will be performed at Screening and only participants with a negative result will be allowed to participate in the study*.
• Only for Stage 1.
• For Malawi (Stage 2), the participant lives in Blantyre and has agreed to remain in Blantyre for the study duration.

Exclusion criteria Medical Conditions

• Known exposure to S. Typhi and nontyphoidal Salmonella confirmed by blood culture during the period starting 3 years prior to first study intervention administration confirmed using past medical history.
• History of any reaction or hypersensitivity associated with any component of the study interventions.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
• Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by physical examination or laboratory screening tests.
• Recurrent history or uncontrolled neurological disorders or seizures.
• Any clinically significant* hematological and/or biochemical laboratory abnormality.
• The Investigator should use his/her clinical judgment to decide which abnormalities are clinically significant from the panel of tests in the list of safety assays.
• Clinical conditions representing a contraindication to IM injections and/or blood draws.
• Any behavioral or cognitive impairment or psychiatric disease that in the opinion of the Investigator, may interfere with the participant's ability to participate in the study.
• Confirmed positive COVID-19 polymerase chain reaction or lateral flow test during the period starting 28 days before the first administration of study vaccines (Day -28 to Day 1).
• Acute or chronic illness which may be severe enough to preclude participation.
• Any other clinical condition that, in the opinion of the Investigator, might pose additional risk to the participant due to participation in the study.
• All medical conditions will be assessed by the Investigator who may use his/her discretion to decide if the participant meets the exclusion criteria.

Prior/Concomitant Therapy

• History of receiving any typhoid vaccine (Ty21a, Vi capsular polysaccharide, or TCV) in the participant's life.
• History of receiving any investigational iNTS or GMMA vaccines in the participant's life.
• Use of any investigational or non-registered product other than the study interventions during the period beginning 30 days (Days -30 to 1) before the first dose of study interventi