This is a phase 1, first-in-human, randomized, double-blind, placebo-controlled, dose-escalation study to evaluate the safety, tolerability, and immunogenicity of VAX-A1 in healthy adults 18-40 years of age.

Inclusion Criteria:

• Individuals 18-40 years of age (inclusive) at the time of randomization into the study
• Able and willing to complete the informed consent process
• Available for clinical follow-up through the last study visit at 6 months post-Dose 2
• Willing to have blood samples collected, stored indefinitely, and be used for research purposes
• Able to provide proof of identity to the satisfaction of the study staff completing the enrollment process
• Healthy, as defined by absence of clinically significant medical condition, either acute or chronic, as determined by medical history, vital signs, physical examination, screening laboratory test results, TTE and ECG results, and clinical assessment by the Investigator
• For applicable individuals, postmenopausal (as confirmed by follicle-stimulating hormone [FSH] level at Screening) for at least 1 year, or surgically sterile for at least 6 months prior to dosing
• Individuals of childbearing potential must be not pregnant and not lactating, must have negative urine and serum pregnancy tests at Screening and a negative urine pregnancy test immediately prior to randomization, and agree to use acceptable contraception if heterosexually active. Participants must agree to consistently practice contraception if sexually active at least 7 days prior to enrollment and throughout the duration of the study
• Able to access and use a smartphone, tablet, computer, or other device connected to Wi-Fi or cellular network for completion of an eDiary

Exclusion Criteria:

• History of any clinically important cardiac, rheumatologic, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, or other disease as determined by the Investigator. This includes a history of polyarthritis, nephropathy, pericarditis, myocarditis, or hypertension requiring current pharmacologic treatment.
• History of invasive GAS infection (such as toxic shock syndrome, necrotizing fasciitis, bloodstream infection, pleural empyema, meningitis) or poststreptococcal immune mediated disease (such as RHD, ARF, or APSGN)
• Known or suspected autoimmune disease, collagen vascular disease, or impairment/alteration of immune function (e.g., congenital or acquired immunodeficiency)
• Previous or existing diagnosis of human immunodeficiency virus, Hepatitis B virus, or Hepatitis C virus, or a positive serologic test at Screening
• History of malignancy or neoplasm, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
• Bleeding disorder diagnosed by a physician (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions) resulting in clinically significant bruising or bleeding difficulties with IM injections or blood draws
• History of severe allergic reaction with generalized urticaria, angioedema, or anaphylaxis to any previous vaccination
• Oral temperature >38.0°C (>100.4°F) or acute illness within 3 days prior to study vaccination (subject may be rescreened)
• Confirmed elevated BP at Screening, defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg measured seated after ≥5 minutes rest and confirmed by repeat measurement
• Physical examination indicating any clinically significant medical condition or inadequate venous access
• Any Grade ≥2 abnormal safety laboratory test at Screening
• Abnormal ESR, or CRP or C3 levels at Screening
• Confirmed microscopic hematuria (>10 RBC/mm³) on UA at Screening. If a potential confounder is present, a repeat UA may be performed during the Screening window; exclusion applies to confirmed microscopic hematuria on an evaluable specimen.
• Evidence of antecedent/recent GAS infection based on anti-DNase B titer ≥ the laboratory reported upper limit of normal (ULN) for the assay used at Screening. Participants with anti-DNase B titer ≥0.8×ULN and \

Vaxcyte is committed to providing access to anonymized data from the company's clinical trials for the purpose of legitimate scientific research. Requests for data may be addressed to datasharing@vaxcyte.com. Requests must be accompanied by a detailed analysis plan and will be reviewed for scientific validity. Sharing of data will require execution of a data-sharing agreement.

Criteria will depend on the specific proposal received and may include qualification of the scientific researchers, potential contribution to the research field, scientific rigor of statistical and analytical methods, and other criteria appropriate for the proposal.