The primary objectives of this study are to evaluate the safety, tolerability, immunologic noninferiority (for shared serotypes) and immunologic superiority (for novel serotypes) of VAX-31 compared to PCV21 and PCV20 in adults ≥50 years of age, and to bridge the immune responses induced by VAX-31 in adults 50-64 years of age to adults 18-49 years of age.

Inclusion Criteria:

• Male or female ≥18 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.
• In good general health or with stable underlying chronic condition(s), as determined by medical history, oral temperature, physical examination, and clinical judgment of the Investigator (ongoing chronic conditions must be documented as stable per Investigator).
• Willing to have blood samples collected and used for research purposes.
• Able to provide proof of identity to the satisfaction of the site personnel completing the enrollment process.
• Female participants of childbearing potential, defined as premenopausal females capable of becoming pregnant, must have a negative urine pregnancy test immediately prior to randomization and agree to use acceptable contraception. Male subjects with partners of childbearing potential must agree to practice an acceptable contraception method.
• Able to access and use a device connected to Wi-Fi or cellular network for completion of an electronic diary (eDiary).

Exclusion Criteria:

• History of invasive pneumococcal disease (IPD) or pneumococcal pneumonia (either confirmed or self-reported) at any age.
• Previous receipt of any licensed or investigational pneumococcal vaccine at any age.
• Receipt of any investigational product within 30 days prior to Day 1, currently participating in another interventional investigational study, or having plans to receive another investigational product(s) while on study.
• Receipt of any live vaccine within 30 days prior to Day 1, or receipt of any non-live (including inactivated) vaccine within 14 days prior to Day 1.
• Body temperature >38.0°C (>100.4°F) or acute illness within 3 days prior to study vaccination (subject may be rescreened).
• Current diagnosis of human immunodeficiency virus, Hepatitis B, or Hepatitis C.
• History of severe allergic reaction with generalized urticaria, angioedema, or anaphylaxis to any previous vaccination.
• Individual who is pregnant, breastfeeding, or planning to become pregnant during study participation.
• Has a known or suspected immunocompromising condition, including, but not limited to, leukemia, lymphoma, chronic renal failure, or congenital or acquired immunodeficiency.
• Bleeding disorder diagnosed by a doctor (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.
• Receipt of blood or blood product (including polyclonal intravenous immunoglobulin) within 60 days prior to enrollment into the study.
• Is currently receiving immunosuppressive or immune-modifying therapy, including systemic corticosteroids (this includes ≥3 months of prednisone equivalent from 5 to <10 mg/day and ≥2 weeks of prednisone equivalent ≥10 mg/day).
• Received any part of a ≥14-day course of systemic corticosteroids (prednisone equivalent >10 mg/day) within 14 days of study vaccination.
• History of malignancy ≤5 years before enrollment, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
• Any medical, psychiatric, or social condition that in the judgment of the Investigator is a contraindication to protocol participation or impairs a subject's ability to give informed consent.
• Employee of, or first-degree relative of, any person employed by the Sponsor, the contract research organization (CRO), the Investigator, site personnel, or site.

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. Data will be made available after initial product approval. Sharing of data may require execution of a data-sharing agreement.

Individual participant data will be shared after deidentification and made available starting 6 months after initial product approval.

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.