BACKGROUND:The AS01E-adjuvanted respiratory syncytial virus (RSV) prefusion F protein-based vaccine (adjuvanted RSVPreF3) is approved for ≥60-year-olds and 50-59-year-olds at increased risk of RSV disease. We evaluated the vaccine's immunogenicity and safety in 18-49-year-olds at increased risk of RSV disease due to certain chronic conditions. METHODS:This open-label, multicountry phase 3b trial included 18-49-year-olds at increased risk (at-risk 18-49 group) and a control group of ≥60-year-olds with or without chronic conditions (≥60 group). Primary objective was to demonstrate immunological noninferiority to adjuvanted RSVPreF3 in the at-risk 18-49 versus ≥60 group, based on group RSV-A/RSV-B geometric mean titer ratios and seroresponse rate differences 1 month postvaccination. Humoral, cell-mediated immunogenicity, and safety were assessed until 6 months postvaccination. RESULTS:Overall, 1458 adults were vaccinated. Immunological noninferiority was demonstrated in the at-risk 18-49 versus ≥60 group at 1 month postvaccination. Both groups showed increased RSV-A/RSV-B neutralizing titers and RSVPreF3-specific CD4+ T-cell frequencies at 1 month postvaccination that declined but remained above baseline at 6 months. Solicited events were more frequent in the at-risk 18-49 (84.3%) than in the ≥60 group (69.4%); most were mild-to-moderate and transient. Rates and intensity of unsolicited adverse events (AEs) were comparable across groups, with low reporting of serious AEs and AEs of special interest. CONCLUSIONS:Adjuvanted RSVPreF3 was immunologically noninferior in 18-49-year-olds with underlying conditions compared with ≥60-year-olds in whom efficacy was previously demonstrated, supporting efficacy inference in this younger population. Up to 6 months postvaccination, the vaccine elicited robust immune responses, and the safety profile was acceptable. Clinical Trial Registration: NCT06389487.
Background: Continuous glucose monitors (CGM) are increasingly being used to manage diabetes. We evaluated the performance and safety of an investigational 15-day G7 integrated CGM (iCGM; Dexcom) in adults with diabetes. Methods: This prospective, multicenter study enrolled adults (age ≥18 years) with type 1 diabetes (T1D) or type 2 diabetes (T2D) at six clinical sites in the United States. Four in-clinic visits were conducted on days 1-3, 4-7, 9-12, and 13-15.5, with frequent arterialized venous blood draws for comparator measurements using a Yellow Springs Instrument (YSI) 2300 Stat Plus glucose analyzer. Participants with T1D or T2D using intensive insulin therapy participated in clinic sessions with deliberate, closely monitored glucose manipulations. Accuracy evaluations included the mean absolute relative difference (MARD), proportion of CGM values within 15 mg/dL of YSI values <70 mg/dL or within 15% of YSI values ≥70 mg/dL (%15/15), as well as %20/20, %30/30, and %40/40 agreement rates. Performance related to iCGM special controls, user experience, and device safety were also assessed. Results: The study enrolled 130 adults with diabetes (mean ± standard deviation age 43.0 ± 14.4 years, 53.1% female, 86.9% with T1D) and analyzed 20,310 CGM-YSI matched pairs from 130 15-day G7 CGM devices. The overall MARD was 8.0% and the %15/15, %20/20, %30/30, and %40/40 agreement rates were 87.7%, 94.2%, 98.9%, and 99.8%, respectively. The device exceeded iCGM performance goals, and user experiences were broadly positive. No serious adverse events were reported. Conclusions: The 15-day G7 iCGM was accurate and safe in adults with diabetes throughout the 15.5-day wear period. Clinicaltrials.gov: NCT05263258.
Background Pneumococcal diseases cause considerable morbidity and mortality in adults. V116 is an investigational 21-valent pneumococcal conjugate vaccine (PCV) specifically designed to protect adults from pneumococcal serotypes responsible for the majority of residual pneumococcal diseases. This phase 3 study evaluated safety, tolerability, and immunogenicity of V116 in pneumococcal vaccine-experienced adults aged >= 50 years.Methods A total of 717 adults were enrolled to receive a single dose of pneumococcal vaccine as follows: cohort 1 (n = 350) previously received 23-valent pneumococcal polysaccharide vaccine (PPSV23) and were randomized 2:1 to receive V116 or PCV15, respectively; cohort 2 (n = 261) previously received PCV13 and were randomized 2:1 to receive V116 or PPSV23, respectively; cohort 3 (n = 106) previously received PPSV23 + PCV13, PCV13 + PPSV23, PCV15 + PPSV23, or PCV15 and all received open-label V116. Immunogenicity was evaluated 30 days postvaccination using opsonophagocytic activity (OPA) geometric mean titers (GMTs) and immunoglobulin G (IgG) geometric mean concentrations (GMCs) for all V116 serotypes. Safety was evaluated as the proportion of participants with adverse events (AEs).Results V116 was immunogenic across all 3 cohorts as assessed by serotype-specific OPA GMTs and IgG GMCs postvaccination for all 21 serotypes. V116 elicited comparable immune responses to serotypes shared with PCV15 (cohort 1) or PPSV23 (cohort 2), and higher immune responses to serotypes unique to V116. The proportions of participants with solicited AEs were generally comparable across cohorts.Conclusions V116 is well tolerated with a safety profile comparable to currently licensed pneumococcal vaccines and generates IgG and functional immune responses to all V116 serotypes, regardless of prior pneumococcal vaccine received.Clinical Trials Registration NCT05420961; EudraCT 2021-006679-41. V116, an investigational 21-valent pneumococcal conjugate vaccine (PCV), was immunogenic for all vaccine serotypes in adults previously vaccinated with a pneumococcal vaccine, with a safety profile generally comparable to 15-valent PCV and 23-valent pneumococcal polysaccharide vaccine. Study results support the use of V116 in adults.
Urinary tract infections (UTI) caused by carbapenem-resistant Enterobacteriaceae (CRE) are considered one of the most urgent health threats to humans according to the Centers for Disease Control (CDC), and the World Health Organization (WHO). A FimCH Vaccine expanded access study is being conducted in patients with a history of antibiotic resistant UTIs who are considered to be at risk for development of CRE UTI. This case series describes the clinical, safety and immunogenicity findings for four participants who received a FimCH four-vaccine series. Participants were followed for 12 months after administration of the fourth vaccine for safety, general health status and UTI occurrence. The study was later amended to allow additional follow-up of up to five years post vaccine administration to assess long-term health status, UTI occurrences and to obtain blood samples for anti-FimH antibody testing. In our population of 4 study participants, the number of symptomatic UTI occurrences caused by gram-negative bacteria in the 12-month period following peak anti-FimH antibody response were approximately 75% lower than the 12-month period preceding study enrollment. These results are consistent with the 30-patient cohort of a Phase 1 study with the same FimCH Vaccine. UTI occurrences increased during the long-term follow-up period for all 4 participants but did not reach the rate observed pre-vaccination. No new safety concerns related to the FimCH Vaccine were identified during long-term follow-up. This case series has clinical importance and public health relevance since it examines and reports on UTI frequency and recurrence following vaccination with the FimCH Vaccine in a high-risk population of patients with recurrent UTI. Additionally, participants described improved well-being following vaccination which was maintained in the long-term follow-up period.
