A randomized, placebo-controlled trial of 13-valent pneumococcal conjugate vaccination to accelerate immune recovery after sepsis
In brief
Pneumococcal vaccine failed to reduce infection-related rehospitalization or death in sepsis survivors
In a randomized trial of 214 ICU sepsis survivors, a single dose of PCV13 did not lower the combined risk of infection-related readmission or mortality over one year compared with placebo, and reinfections actually occurred more often in the vaccine group. Immunogenicity was variable and no safety concerns emerged, highlighting the need for other strategies to address post-sepsis immune dysfunction.
- Journal
- Science translational medicine (Q1)
- Published
- 12 August 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Manu Shankar-Hari, Peter Smith, Tamas Szakmany, Charlotte Summers, Peter J McGuigan, David Brealey, et al.
- PMID
- 42585292
- DOI
- 10.1126/scitranslmed.aeb4113
Why clinicians should know about it
- Picked for Critical Care and Intensive Care Medicine (top studies of the week, 16 August 2026): PCV13 vaccine trial in sepsis survivors (post‑ICU)
Abstract
Adults who survive intensive care unit (ICU) admission with sepsis (sepsis survivors) have immune impairments involving concurrent inflammation and immunosuppression that increase their long-term risk of reinfections and mortality. Vaccine immunogenicity could therefore be abnormal in sepsis survivors but has never been examined. Here, in a 1:1 randomized, placebo-controlled trial, we tested the efficacy and immunogenicity of a single intramuscular dose of 13-valent pneumococcal conjugate vaccine (PCV13) in 214 sepsis survivors at ICU discharge. The PCV13 group (n = 104) experienced 43 primary outcome events (time to first infection-related rehospitalization or death during 365 days of follow-up) among 72.5 person-years of follow-up compared with 38 events among 76.5 person-years of follow-up in the placebo group (n = 110) [hazard ratio, 1.23 (95% CI, 0.80 to 1.91)]. The PCV13 group experienced higher rates of reinfections and received earlier antibiotic prescriptions in primary care. There were no vaccine-related serious adverse events. PCV13 immunogenicity assessments included serotype-specific immunoglobulin G (IgG), immunophenotyping, and pan-leukocyte RNA sequencing measured at baseline and 10 and 30 days postrandomization. PCV13-induced serotype-specific IgG responses varied across serotypes and participants, without excessive cytokine responses. PCV-induced blood transcriptional module responses in antigen-presenting cells and helper T cells were also variable. Variations in PCV13 immunogenicity were associated with age in men, body mass index in women, and cytotoxicity-associated gene modules regardless of sex. This trial showed that PCV13 administered at ICU discharge did not benefit this sepsis survivor population and underscores the need for further research to delineate treatable molecular mechanisms of postsepsis immune dysfunction (ClinicalTrials.gov identifier NCT03565159).
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.