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

## TL;DR

This study examines how allogeneic stem cell transplant patients respond to pneumococcal vaccines, finding that initial conjugate vaccines prime immunity while polysaccharide boosters may weaken prior responses.

## Contribution

First integrated analysis of humoral and T-cell responses to pneumococcal vaccination in allogeneic HSCT recipients.

## Key findings

- Conjugate vaccination primes CD4+ T-cell proliferation and T-cell memory.
- Polysaccharide boosting broadens serotype coverage but may reduce antibody titers for shared serotypes.
- Sequential vaccination induces a T-helper 17 cytokine response without expanding functional immune memory.

## Abstract

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.

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.

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.

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.