The objective of the study is to evaluate the safety and tolerability of a single injection of VAX-24 at 3 dose levels compared to Prevnar 20™ (PCV20) in adults 65 years of age and older.

The objective of the study is to evaluate the safety and tolerability of a single injection of VAX-24 at 3 dose levels (Low: 1.1 mcg; Mid: 2.2 mcg; or Mixed: 2.2/4.4 mcg) compared to Prevnar 20™ (PCV20) in adults 65 years of age and older.

Inclusion Criteria:

• Male or female age 65 or older.
• Able and willing to complete the informed consent process.
• Available for clinical follow-up through the last study visit at 6 months after the study vaccination.
• In good general health as determined by medical history, vital signs, physical examination, and clinical judgment of the investigator. Preexisting medical conditions must be stable as defined by no change in treatment at least 6 weeks prior to study participation.
• Willing to have blood samples collected, stored indefinitely, and used for research purposes.
• Able to provide proof of identity to the satisfaction of the study staff completing the enrollment process.

Exclusion Criteria:

• Previous pneumococcal disease (either confirmed or by self-reporting).
• Previous receipt of a licensed or investigational pneumococcal vaccine.
• Receipt of any investigational study product within 30 days prior to enrollment into the study, currently participating in another interventional investigational study, or having plans to receive another investigational product(s) while on study.
• Planned or actual administration of any licensed vaccine during the period starting 30 days before enrollment into the study through Day 29.
• Physical examination indicating any clinically significant medical condition.
• Body Temperature > 38.0°C (> 100.4°F) or acute illness within 3 days prior to study vaccination (subject may be rescheduled).
• Previous or existing diagnosis of HIV, Hepatitis B or Hepatitis C.
• History of severe allergic reaction with generalized urticaria, angioedema, or anaphylaxis.
• Bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with intramuscular injections or blood draws.
• Any other chronic or clinically significant medical condition that, in the opinion of the investigator, would jeopardize the safety or rights of the subject or confound evaluation of the study vaccine.
• 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.
• Received blood or blood product (including Immune Globulin IV) within 90 days prior to enrollment into the study.
• Received systemic corticosteroids for ≥ 14 consecutive days and has not completed treatment ≤30 days prior to enrollment into the study.
• Receiving immunosuppressive therapy.
• History of malignancy ≤5 years before enrollment, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.

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.

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Triple (Participant, Investigator, Outcomes Assessor)

Sponsor shall review within the ninety (90) day period. Upon receiving any notification from Sponsor requesting deletion of Confidential Information, correction of inaccuracies, or a delay in publication to allow the filing of patent application, Institution or Investigator shall take the requested action of Sponsor.