Integrated analysis of humoral and T-cell responses to pneumococcal vaccination in allogeneic hematopoietic stem cell transplant recipients

Introduction Allogeneic hematopoietic stem cell transplant (HSCT) recipients remain highly susceptible to pneumococcal infection despite current vaccination strategies, and the contribution of T-cell–mediated immunity to protection in this population is not fully defined. Methods We conducted a prospective study evaluating humoral and cellular immune responses to sequential pneumococcal vaccination with the 13-valent conjugate vaccine (PCV13) followed by the 23-valent polysaccharide vaccine (PPV23) in allogeneic HSCT recipients. Immune responses were assessed through serotype-specific antibody quantification, CD4 + T-cell proliferation assays, and cytokine profiling after in vitro stimulation with heat-killed Streptococcus pneumoniae . Results Conjugate vaccination induced antigen-specific CD4 + T-cell proliferation and established T-cell memory. However, subsequent polysaccharide vaccination did not enhance CD4 + T-cell proliferation in sequentially vaccinated patients. PPV23 administration was associated with a decline in antibody titers for serotypes shared with the conjugate vaccine, while humoral responses to non-shared serotypes were preserved. Despite the lack of cellular boosting, the sequential schedule elicited a strong T-helper 17 cytokine response, characterised by increased secretion of interleukin-17A, interleukin-17F, and interleukin-22, suggesting activation of a pro-inflammatory pathway rather than expansion of functional immune memory. Discussion This study provides, to our knowledge, the first integrated analysis of both humoral and T-cell immune responses to pneumococcal vaccination in allogeneic HSCT recipients, offering a translational perspective that links immunological mechanisms with clinical relevance. Our findings indicate that conjugate vaccination is essential for priming both cellular and humoral immunity, whereas polysaccharide boosting primarily broadens serotype coverage but may attenuate previously established immune responses. In the context of emerging higher-valency conjugate vaccines, including the recently introduced 21-valent formulation incorporating novel serotypes, these results support a reassessment of the need for polysaccharide boosters and inform optimisation of pneumococcal vaccination strategies in immunocompromised hosts at high risk for invasive disease.