A Phase 3, randomized, modified double-blind, active-controlled, parallel-group, 2-arm study to investigate the safety and immunogenicity of a single dose of a 21-valent pneumococcal conjugate vaccine in children and adolescents ages 2-17 with sickle cell disease. The 21-valent pneumococcal conjugate vaccine (PCV21) is an investigational vaccine designed to offer broad protection against pneumococcal disease. It includes 21 serotypes—20 shared with the 20-valent PCV Prevnar 20TMa (20vPCV) plus one additional serotype (9N). These serotypes are conjugated to two carrier proteins: tetanus toxoid (TTxd) or a non-toxic mutant of diphtheria toxin (CRM197). Currently enrolling at multiple U.S. sites and in the DR.