This study tests a new vaccine called **PCV21** to see if it is safe and helps kids with **sickle cell disease** (SCD) make antibodies to fight germs. Sickle cell disease is a condition where red blood cells, which carry oxygen, are shaped like a sickle and can block blood flow. The study compares PCV21 with another vaccine, **20vPCV**, in children aged 2 to 17 who may or may not have received prior pneumococcal vaccines. **Pneumococcal vaccines** help protect against infections caused by a type of bacteria called pneumococcus. **Study Details**: - **Duration**: Up to 6 months per participant. - **Eligibility**: Must be 2 to 17 years old with documented SCD, not pregnant or breastfeeding, and willing to follow study rules. - **Exclusions**: Includes recent vaccine or treatment history, certain health conditions, and participation in other studies. This study helps determine if PCV21 is effective and safe for children with SCD. Participants must attend all study visits and follow the procedures. The study ensures that children and their guardians understand and agree to participate.