GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE317nnn/GSE317767/primary200OKTranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE317767GEOGSEfalse13-Valent Pneumococcal Conjugate Vaccination to Accelerate Immune Recovery in Sepsis Survivors: a randomized placebo-controlled trial with embedded immunobiologyAdults who survive intensive care unit (ICU) admission with sepsis (referred to as sepsis survivors) have immune impairments that increase their long-term risk of reinfections and mortality. Although vaccinations may reverse immune impairments, vaccine immunogenicity has never been examined in sepsis survivors. 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. The primary outcome was time to first infection-related rehospitalization or death during 365 days of follow-up. PCV13 immunogenicity assessments included serotype-specific immunoglobulin-G (IgG) concentrations, immunophenotyping and panleukocyte transcriptome, measured at baseline(T0), 10(±3)days(T1), and 30(±7)days(T2) post-randomization. The PCV13 group (n=104) had 43 primary outcome events 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,0.80-1.91)]. There were no vaccine-related serious adverse events. PCV13 induced serotype-specific IgG responses, exhibiting variations across serotypes and participants. Additionally, there were changes in blood transcriptional modules and pre-vaccination inflammatory endotypes that explain this variation in IgG responses. Of note, clinical outcomes were better albeit not statistically significant, in participants with ≥2-fold increase in ≥2 serotype-specific IgG. Better understanding of variations in vaccine immunogenicity in sepsis survivors is crucial for improving long-term outcomes. 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