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BACKGROUND Respiratory syncytial virus (RSV) is an important cause of acute respiratory infection, lower respiratory tract disease, clinical complications, and death in older adults. There is currently no licensed vaccine against RSV infection. METHODS In an ongoing, international, placebo-controlled, phase 3 trial, we randomly assigned, in a 1:1 ratio, adults 60 years of age or older to receive a single dose of an AS01E-adjuvanted RSV prefusion F protein-based candidate vaccine (RSVPreF3 OA) or placebo before the RSV season. The primary objective was to show vaccine efficacy of one dose of the RSVPreF3 OA vaccine against RSV-related lower respiratory tract disease, confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR), during one RSV season. The criterion for meeting the primary objective was a lower limit of the confidence interval around the efficacy estimate of more than 20°6. Efficacy against severe RSV-related lower respiratory tract disease and RSV-related acute respiratory infection was assessed, and analyses according to RSV subtype (A and B) were performed. Safety was evaluated. RESULTS A total of 24,966 participants received one dose of the RSVPreF3 OA vaccine (12,467 participants) or placebo (12,499). Over a median follow-up of 6.7 months, vaccine efficacy against RT-PER-confirmed RSV-related lower respiratory tract disease was 82.6% (96.95% confidence interval [CI], 5Z9 to 94.1), with 7 cases (1.0 per 1000 participant-years) in the vaccine group and 40 cases (5.8 per 1000 participant-years) in the placebo group. Vaccine efficacy was 94.1% (95% CI, 62.4 to 99.9) against severe R.SV-related lower respiratory tract disease (assessed on the basis of clinical signs or by the investigator) and 71.7% (95% CI, 56.2 to 82.3) against RSV-related acute respiratory infection. Vaccine efficacy was similar against the RSV A and B subtypes (for RSV-related lower respiratory tract disease: 84.6% and 80.9°6, respectively; for RSV-related acute respiratory infection: 71.9% and 70.6%, respectively). High vaccine efficacy was observed in various age groups and in participants with coexisting conditions. The RSVPreF3 OA vaccine was more reactogenic than placebo, but most adverse events for which reports were solicited were transient, with mild-to-moderate severity. The incidences of serious adverse events and potential immune-mediated diseases were similar in the two groups. CONCLUSIONS A single dose of the RSVPreF3 OA vaccine had an acceptable safety profile and prevented KSV-related acute respiratory infection and lower respiratory tract disease and severe RSV-related lower respiratory tract disease in adults 60 years of age or older, regardless of RSV subtype and the presence of underlying coexisting conditions. (Funded by GlaxoSmithKline Biologicals; AReSVi-006 ClinicalTrials.gov number, NCT04886596.). [ABSTRACT FROM AUTHOR]

Abstract: Background: Pneumocystis jirovecii pneumonia (PJP) affected 5%‐15% of solid organ transplant (SOT) recipients prior to universal prophylaxis, classically with trimethoprim‐sulfamethoxazole (TMP‐SMX). Guidelines generally recommend 6‐12 months of prophylaxis post‐SOT, yet optimal duration and robust PJP risk stratification have not been established. Methods: A retrospective, single‐center, case‐control study of PJP among SOT recipients from January 1998 to December 2013 was conducted. Cases had positive PJ direct fluorescent antibody assay of respiratory specimens. Controls were matched 4:1 by nearest date of SOT. Univariate testing and multivariate logistic regressions were performed. Results: Fifteen cases were identified among 5505 SOT recipients (0.27% rate) and analyzed vs 60 controls. PJP occurred on average 6.1 years (range 0.9‐13.8) post‐SOT; no case was receiving PJP prophylaxis at diagnosis. Most were treated with reduced immunosuppression and TMP‐SMX plus steroids (80%). Six patients (40%) required critical care; 3 (20%) died. There were no significant demographic differences, though cases tended to be older at SOT (54 vs 48 years, P = .1). In univariate analysis, prior viral infection was more common among cases (67% vs 37%, P = .08). Lower absolute lymphocyte count (ALC) at diagnosis date was strongly associated with PJP (400 vs 1230 × 106 cells/μL, P < .001); odds of infection were high with ALC ≤ 500 × 106 cells (OR 18.7, P < .01). Conclusion: Pneumocystis jirovecii pneumonia is a rare, late complication of SOT with significant morbidity and mortality. Severe lymphopenia may be useful in identifying SOT recipients who warrant continued or reinstated PJP prophylaxis. [ABSTRACT FROM AUTHOR]