INTRODUCTION:Children with solid organ transplants (SOT) face higher risks of severe disease from varicella-zoster virus (VZV). Although some guidelines recommend live attenuated varicella vaccine (LAVV) for select children post SOT, further real-world vaccine immunogenicity and safety data are needed. METHODS:A prospective observational study was conducted at 4 Canadian centres from 2020 to 2023. Children who were 1-19 years, VZV IgG negative, > 1 year post liver, kidney, or heart transplant, and were receiving LAVV as part of clinical care in accordance with centre-specific criteria were eligible for inclusion. Measurement of VZV IgG was recommended post-vaccination with LAVV. Adverse events following immunization (AEFIs) were captured via telephone survey and chart review. RESULTS:Fifty-six pediatric SOT recipients (51 liver, 3 kidney, and 2 heart) received ≥ 1 dose of LAVV. Serology after the last post-transplant dose of LAVV was available for 43/56 (77%) participants; 39/43 (91%) seroconverted to positive VZV IgG (12/16 after 1 post-transplant dose, 26/30 after 2 doses and 1/1 after 3 doses). Among 56 dose 1 recipients, 6 (11%) experienced an AEFI requiring medical attention. Four had rash: 3 with varicella-like rash (1/3 confirmed vaccine-strain varicella) and none required antivirals. Two had acute rejection 4-5 weeks after LAVV. Two of 38 (5%) dose 2 recipients had an AEFI requiring medical attention, with one serious AEFI 7 weeks after LAVV that was not deemed vaccine-related after careful review. CONCLUSIONS:LAVV was immunogenic and generally well tolerated in our cohort of patients. Post-SOT LAVV should be considered for select VZV seronegative children with close follow-up.

Importance:Clesrovimab is a long-acting monoclonal antibody approved for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants who are born during or entering their first RSV season; data concerning clesrovimab from a second RSV season among children who remain at risk for severe disease are needed. Objective:To evaluate the safety and tolerability of clesrovimab (105 mg) vs palivizumab in RSV season 1 in infants at increased risk for severe RSV disease. Key secondary objectives include describing the safety of 210 mg of clesrovimab in RSV season 2 in children who remain at increased risk for severe RSV disease, clesrovimab pharmacokinetics, and the incidence of RSV-associated disease. Design, Setting, and Participants:SMART (MK-1654-007) was a randomized, partially masked, palivizumab-controlled, phase 3 clinical trial, conducted at 110 sites in 27 countries and territories between November 30, 2021, and November 20, 2025. The population constituted palivizumab-eligible infants, including those with prematurity, chronic lung disease of prematurity, or hemodynamically significant congenital heart disease. Interventions:Participants, randomized 1:1 and stratified by region and condition, received clesrovimab (105 mg) on day 1 followed by placebo on day 28 or monthly palivizumab (15 mg/kg) up to 5 doses (1 dose per month). Eligible infants received open-label clesrovimab (210 mg) before their second RSV season. Main Outcomes and Measures:The primary outcome was the observed proportions of participants experiencing adverse events (AEs) after clesrovimab or palivizumab in season 1. Results:Overall, 997 infants (500 [50.2%] male; median age, 2.6 [range, 0.0-12.0] months) received clesrovimab, 105 mg (n = 498) or palivizumab (n = 499) in season 1; 276 received clesrovimab, 210 mg open-label in season 2. In season 1, the proportions of participants experiencing AEs were comparable between treatment groups. In season 2, clesrovimab, 210 mg was well tolerated. Incidence rates of RSV-associated medically attended lower respiratory infection (MALRI) were comparable between clesrovimab and palivizumab (3.2% [95% CI, 1.8%-5.2%] and 3.4% [95% CI, 2.0%-5.6%], respectively) through day 150 in season 1; total RSV-associated MALRI incidence through day 180 after a 210-mg dose in season 2 was 7.3% (95% CI, 4.4%-11.4%). Conclusions and Relevance:In this randomized clinical trial, clesrovimab was well tolerated in infants at increased risk for severe RSV disease through 2 RSV seasons. These findings support the use of clesrovimab in children who remain at risk for severe RSV disease in their second RSV season. Trial Registration:ClinicalTrials.gov Identifier: NCT04938830.

OBJECTIVE:To evaluate descriptive efficacy data, exploratory immunogenicity data, and safety follow-up through study completion from the global, phase 3 MATISSE (Maternal Immunization Study for Safety and Efficacy) maternal vaccination trial of bivalent respiratory syncytial virus (RSV) prefusion F protein vaccine (RSVpreF). METHODS:MATISSE was a phase 3, randomized, double-blinded, placebo-controlled trial. Healthy pregnant participants aged 49 years or younger at 24-36 weeks of gestation were randomized (1:1) to receive a single RSVpreF 120 micrograms or placebo dose. Primary efficacy endpoints included newborn and infant severe RSV-associated medically attended lower respiratory tract illness within 180 days after birth. The RSV-A and RSV-B serum neutralizing antibody titers were determined in a subset of pregnant participants and their newborns. RESULTS:In this final analysis, 7,420 pregnant participants were randomized, and 7,307 children were born (RSVpreF n=3,660, placebo n=3,647). Vaccine efficacy , defined as protection against newborn and infant severe RSV-associated medically attended lower respiratory tract illness, was 82.4% (95% CI, 57.5-93.9) and 70.0% (95% CI, 50.6-82.5) within 90 and 180 days of birth, respectively. The RSVpreF induced robust immune responses in pregnant participants and resulted in highly efficient transfer of maternal antibodies to their newborns across subgroups (by gestational age at delivery and at vaccination, number of days from vaccination to delivery, country, maternal age). Final RSVpreF safety results in pregnant and newborn and infant participants were consistent with the primary analysis with no new safety concerns identified. CONCLUSION:This final analysis of MATISSE trial data confirms the primary analysis conclusions: Maternal vaccination with RSVpreF has a favorable safety profile in both pregnant and newborn and infant participants and demonstrates efficacy against RSV-associated lower respiratory tract illness in infants through age 6 months. The RSVpreF induces robust immune responses in pregnant individuals, with corresponding high RSV-neutralizing titers in their newborns. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov , NCT04424316.

Importance Clesrovimab is a long-acting monoclonal antibody approved for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants who are born during or entering their first RSV season; data concerning clesrovimab from a second RSV season among children who remain at risk for severe disease are needed. Objective To evaluate the safety and tolerability of clesrovimab (105 mg) vs palivizumab in RSV season 1 in infants at increased risk for severe RSV disease. Key secondary objectives include describing the safety of 210 mg of clesrovimab in RSV season 2 in children who remain at increased risk for severe RSV disease, clesrovimab pharmacokinetics, and the incidence of RSV-associated disease. Design, Setting, and Participants SMART (MK-1654-007) was a randomized, partially masked, palivizumab-controlled, phase 3 clinical trial, conducted at 110 sites in 27 countries and territories between November 30, 2021, and November 20, 2025. The population constituted palivizumab-eligible infants, including those with prematurity, chronic lung disease of prematurity, or hemodynamically significant congenital heart disease. Interventions Participants, randomized 1:1 and stratified by region and condition, received clesrovimab (105 mg) on day 1 followed by placebo on day 28 or monthly palivizumab (15 mg/kg) up to 5 doses (1 dose per month). Eligible infants received open-label clesrovimab (210 mg) before their second RSV season. Main Outcomes and Measures The primary outcome was the observed proportions of participants experiencing adverse events (AEs) after clesrovimab or palivizumab in season 1. Results Overall, 997 infants (500 [50.2%] male; median age, 2.6 [range, 0.0-12.0] months) received clesrovimab, 105 mg (n = 498) or palivizumab (n = 499) in season 1; 276 received clesrovimab, 210 mg open-label in season 2. In season 1, the proportions of participants experiencing AEs were comparable between treatment groups. In season 2, clesrovimab, 210 mg was well tolerated. Incidence rates of RSV-associated medically attended lower respiratory infection (MALRI) were comparable between clesrovimab and palivizumab (3.2% [95% CI, 1.8%-5.2%] and 3.4% [95% CI, 2.0%-5.6%], respectively) through day 150 in season 1; total RSV-associated MALRI incidence through day 180 after a 210-mg dose in season 2 was 7.3% (95% CI, 4.4%-11.4%). Conclusions and Relevance In this randomized clinical trial, clesrovimab was well tolerated in infants at increased risk for severe RSV disease through 2 RSV seasons. These findings support the use of clesrovimab in children who remain at risk for severe RSV disease in their second RSV season. Trial Registration ClinicalTrials.gov Identifier: NCT04938830

Pneumococcal disease (PD) causes significant illness and death, especially in young children, older adults, and individuals with chronic medical conditions. Due to increased risk, children with chronic conditions are often advised to receive additional pneumococcal vaccination beyond the routine primary series. This phase 3 study evaluated the safety and immunogenicity of V116, a 21-valent pneumococcal conjugate vaccine, compared to PPSV23 in children aged 2 to <18 y with certain medical conditions that increase risk of PD who had previously completed a primary pneumococcal vaccination regimen. Individuals with diabetes mellitus, chronic heart, chronic lung, chronic kidney, and/or chronic liver disease were randomized 3:2 to receive a single dose of either V116 (n = 531) or PPSV23 (n = 351). Immunogenicity was assessed at 30 d postvaccination comparing opsonophagocytic activity (OPA) geometric mean titers (GMTs) and immunoglobulin G (IgG) geometric mean concentrations (GMCs) between groups. Safety was evaluated by the proportion of participants with adverse events (AEs). The V116 group met the statistical noninferiority criterion for each of the 12 pneumococcal vaccine serotypes shared between V116 and PPSV23 and additionally met superiority criterion for each of the 9 serotypes unique to V116 based on OPA GMTs. IgG GMCs were consistent with the OPA results. The safety profile was generally comparable between groups. In children and adolescents aged 2 to <18 y with certain medical conditions, V116 is well tolerated and immunogenic. These findings support the use of V116 to broaden pneumococcal serotype coverage in populations at increased risk of pneumococcal disease.

Abstract Background Clesrovimab is an investigational, long-acting monoclonal antibody for the prevention of RSV lower respiratory tract infection (LRI) in infants, including those at high risk of severe RSV disease due to serious comorbidity or premature birth. Methods This is a planned interim analysis (IA) of a randomized, controlled, phase 3 trial in infants entering their first RSV season recommended to receive palivizumab due to prematurity (≤35 weeks gestational age), chronic lung disease (CLD) of prematurity, or hemodynamically significant congenital heart disease (CHD). Participants (pts) were randomized 1:1 to receive clesrovimab (105 mg IM on day 1, placebo on day 28) or monthly palivizumab in season 1; eligible pts received clesrovimab (210 mg IM) in season 2 (Figure 1). The primary endpoint was safety and tolerability of clesrovimab vs. palivizumab in season 1. Secondary endpoints included the incidence of RSV-associated medically attended LRI (MALRI) requiring ≥1 indicator of LRI or severity and of RSV-associated hospitalization through day 150. Clesrovimab serum PK was analyzed through day 150. Results At this IA, 901 pts had been randomized into the trial. Baseline characteristics were well balanced; 28% had CLD, 11% had CHD, and 61% were born preterm without CLD/CHD. In season 1, the proportion of pts with AEs were comparable between arms; no pts in the clesrovimab arm had a drug-related serious AE (Table 1). In the season 2 IA, proportions of pts with AEs were comparable between those who had received clesrovimab or palivizumab in season 1. There were 8 deaths (1.8%) in the clesrovimab and 4 (0.9%) in the palivizumab arm, all attributable to underlying comorbidities or causes unrelated to treatment. No anaphylaxis/hypersensitivity reactions were reported. Incidence rates of RSV-associated MALRI and of RSV-associated hospitalization were comparable between clesrovimab (3.6% and 1.3%, respectively) and palivizumab (3.0% and 1.5%, respectively) through day 150 (Table 2). In season 1, the geometric mean half-life of clesrovimab was 44.1 days (Table 3). Conclusion Clesrovimab was well tolerated in infants at high risk for RSV disease. In season 1, a single dose of clesrovimab had a safety profile and RSV disease incidence rates that were generally comparable to monthly palivizumab. Disclosures Heather J. Zar, PhD, MSD, Pfizer, AstraZeneca, Moderna (DSMB): Advisor/Consultant|MSD, Pfizer, AstraZeneca, Moderna (DSMB): Grant/Research Support|MSD, Pfizer, AstraZeneca, Moderna (DSMB): Honoraria|MSD, Pfizer, AstraZeneca, Moderna (DSMB): MSD Principal Investigator for the study and on MSD Advisory Board Louis J. Bont, MD, Pfizer, AstraZeneca, Sanofi, Janssen, MeMed Diagnostics, Gates Foundation, GSK, Novavax, Julius Clinical, Ablynx, Bavaria Nordic, Moderna, and MSD: Advisor/Consultant|Pfizer, AstraZeneca, Sanofi, Janssen, MeMed Diagnostics, Gates Foundation, GSK, Novavax, Julius Clinical, Ablynx, Bavaria Nordic, Moderna, and MSD: Board Member|Pfizer, AstraZeneca, Sanofi, Janssen, MeMed Diagnostics, Gates Foundation, GSK, Novavax, Julius Clinical, Ablynx, Bavaria Nordic, Moderna, and MSD: Grant/Research Support|Pfizer, AstraZeneca, Sanofi, Janssen, MeMed Diagnostics, Gates Foundation, GSK, Novavax, Julius Clinical, Ablynx, Bavaria Nordic, Moderna, and MSD: Honoraria|Pfizer, AstraZeneca, Sanofi, Janssen, MeMed Diagnostics, Gates Foundation, GSK, Novavax, Julius Clinical, Ablynx, Bavaria Nordic, Moderna, and MSD: Regular interaction with pharmaceutical & other industrial partners.Founding chairman-ReSViNET Foundation.Received minor institutional funding to UMCU Paolo Manzoni, MD, PhD, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): Advisor/Consultant|Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): SAC member for MSD Flor M. Munoz, MD, MSc, Pfizer, DMC-Moderna, Meissa, Sanofi, AstraZeneca, Novavax, Gilead, MSD: Advisor/Consultant|Pfizer, DMC-Moderna, Meissa, Sanofi, AstraZeneca, Novavax, Gilead, MSD: Grant/Research Support|Pfizer, DMC-Moderna, Meissa, Sanofi, AstraZeneca, Novavax, Gilead, MSD: SAC member for MSD Octavio Ramilo, MD, Pfizer, Sanofi, Gates Foundation, NIH, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): Advisor/Consultant|Pfizer, Sanofi, Gates Foundation, NIH, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): Grant/Research Support|Pfizer, Sanofi, Gates Foundation, NIH, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): Honoraria|Pfizer, Sanofi, Gates Foundation, NIH, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): SAC member for MSD Po-Yen Chen, MD, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): Princial Investigator for MSD Jose M. Novoa Pizarro, MD, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): Principal Investigator for the study for MSD Gustavo A. Ordonez, MD, Megalabs, Tecnoquimicas SA and MSD: Grant/Research Support|Megalabs, Tecnoquimicas SA and MSD: Honoraria|Megalabs, Tecnoquimicas SA and MSD: Principal Investigator for the study for MSD Maria Tsolia, MD, PhD, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): Princial Investigator for MSD Bruce Tapiero, MD, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): Princial Investigator for MSD Mirta Acuña, MD, Pfizer, Janssen, Sanofi, and MSD: Advisor/Consultant|Pfizer, Janssen, Sanofi, and MSD: Grant/Research Support|Pfizer, Janssen, Sanofi, and MSD: Principal Investigator for Janssen, Sanofi and MSD Javier M. Castellanos, MD, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): Princial Investigator for MSD Michael Meyer, MD, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): Princial Investigator for MSD Ichiro Morioka, MD, PhD, AstraZeneca K.K.: Honoraria|Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): Honoraria|Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): Princial Investigator for MSD|Mitsubishi Tanabe Pharma Corporation: Honoraria|Pfizer Japan Inc.: Honoraria|Sanofi K.K.: Honoraria|Shino-Test Corporation: Grant/Research Support Ziqiang Chen, PhD, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): Employee|Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): Stocks/Bonds (Public Company) Radha A. Railkar, PhD, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, US (MSD): Employee|Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, US (MSD): Stocks/Bonds (Public Company) Xiaowei Zang, PhD, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): Employee|Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): Stocks/Bonds (Public Company) Andrea L. Krick, PhD, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): Employee|Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): Stocks/Bonds (Public Company) Andrew W. Lee, MD, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): Employee at the time of study|Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): Stocks/Bonds (Public Company) Luis A. Castagnini, MD, MPH, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): Employee|Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): Stocks/Bonds (Public Company) Anushua Sinha, MD, MPH, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): Employee|Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): Stocks/Bonds (Public Company)

Background:Outpatient parenteral antimicrobial therapy (OPAT) is often used for patients who need long-term antimicrobial therapy. Meropenem is a broad-spectrum antibiotic used to treat polymicrobial and multidrug-resistant bacterial infections. Objective:To evaluate the efficacy, tolerance, and safety of IV meropenem for pediatric patients in the OPAT program at CHU Sainte-Justine in Montréal, Quebec. Methods:At the study institution, meropenem solutions (1-40 mg/mL) are prepared in polyvinylchloride bags or cassettes. Each delivery device contains one daily dose, and infusions (at room temperature) take place every 8 hours. Devices are delivered to the patient's home in batches every 3 or 4 days. With refrigeration, the drug solution has a short period of stability (96 hours). This single-centre retrospective study included all patients under 18 years of age who received IV meropenem therapy as part of the OPAT program between April 2000 and April 2024. For the current analysis, demographic data, clinical data, serum alanine aminotransferase levels, and white blood cell counts were collected using a standardized template. Results:A total of 349 courses of therapy (for 262 patients) met the inclusion criteria. For most patients, the treatments were successful and well tolerated, with an overall success rate of 93.4% (326/349). Few gastrointestinal symptoms and rashes were reported. Neutropenia and eosinophilia were more frequently observed than in previous studies. OPAT-related adverse events were mainly catheter-related (8.9%, 31/349) or pump-related (6.3%, 22/349) issues. Conclusions:These results suggest that IV meropenem can be safely and effectively used in pediatric OPAT, although the target concentration of 90% may not be retained, according to current stability data.

Invasive meningococcal disease, caused by the bacterium Neisseria meningitidis, is life-threatening but can be prevented with vaccination. There are effective vaccines against different meningococcal serogroups, including serogroup B. Evidence from immunization programs with the 4-component meningococcal serogroup B vaccine, 4CMenB, over the past decade confirms its effectiveness and positive impact against serogroup B disease in people of all age groups. To assess the performance of serogroup B vaccines in clinical trials, tests are required that take into account the wide diversity of serogroup B strains circulating in the population. In this study, the performance of 4CMenB was evaluated using the enc-hSBA assay, which uses the complement (proteins) present in each vaccinated person's blood and is used to test a large number of N meningitidis strains, thereby determining breadth of immune response, based on the vaccine's killing activity against diverse strains. Using this assay, our results showed breadth of immune response following administration of 4CMenB (2 doses, 2 or 6 months apart) against the 110 serogroup B strains tested that was consistent with its performance in immunization programs, with no additional benefit from administering 3 4CMenB doses over the 6-month period. The safety of 4CMenB was consistent with its known safety profile.Clinical Trial Registration. NCT04502693.

In the province of Quebec, Canada, a 2 + 1 dose pneumococcal conjugate vaccine (PCV) program for children was implemented in 2004. PCV7, PCV10, PCV13 and a mixed PCV10/PCV13 schedule were sequentially used without catch-up. The effectiveness of vaccination schedules to prevent serotype 19A invasive pneumococcal disease (IPD) in <5-year-old children was estimated by the indirect cohort method during 2009-2023. A total of 248 19A IPD cases and 457 IPD controls were included in the analysis. Adjusted vaccine effectiveness (VEa) for >= 1 dose was 57 % [95 %CI: -1 %,82 %] for PCV10 and 62 % [16 %,83 %] for PCV13. VEa for 3 doses was 69 % [17 %,88 %] for PCV10, 76 % [39 %,90 %] for PCV13 and 86 % [64 %,95 %] for the 2PCV10 + 1PCV13 schedule. Protection provided by the PCV10-only schedule tended to be of lower magnitude compared to the two other schedules. The mixed PCV10 + PCV13 schedule showed a protection against 19A IPD at least comparable to that of 3 PCV-13 doses.

Introduction An infected popliteal pseudoaneurysm has never been described in the pediatric population. Physicians need to be aware of its presentation and management, in order to diagnose and treat this medical condition adequately. Methods We describe the case of a 14-year-old boy who developed myositis and cellulitis centered at the popliteal fossa after playing basketball. A treatment of intravenous cefazolin was started. 5 days later, he experienced a knee pain flare-up, which turned out to be a popliteal pyomyositis with a pseudoaneurysm of the popliteal artery. A saphenous vein graft bypass of the popliteal artery and an excision of the popliteal pseudoaneurysm were performed. Intravenous cefazolin was continued for 6 weeks and prophylactic acetylsalicylic acid for 6 months. Results and conclusion This case highlighted the importance of repeating radiologic investigations if a patient suffering from soft tissue infection has persistent pain after several days of appropriate antibiotics. A popliteal pseudoaneurysm can be diagnosed with ultrasound imaging and treated with a popliteal-popliteal bypass. Our patient needed a catheter-guided dilation of the anastomosis at the vein graft 6 months post-surgery, and then evolved favorably and went back to playing basketball 6 months post-dilation.

Background. Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in infants. This phase 1/2, observer-blind, randomized, controlled study assessed the safety and immunogenicity of an investigational chimpanzee-derived adenoviral vector RSV vaccine (ChAd155-RSV, expressing RSV F, N, and M2-1) in infants. Methods. Healthy 6- to 7-month-olds were 1:1:1-randomized to receive 1 low ChAd155-RSV dose (1.5 x 10(10) viral particles) followed by placebo (RSV_1D); 2 high ChAd155-RSV doses (5 x 10(10) viral particles) (RSV_2D); or active comparator vaccines/placebo (comparator) on days 1 and 31. Follow-up lasted approximately 2 years. Results. Two hundred one infants were vaccinated (RSV_1D: 65; RSV_2D: 71; comparator: 65); 159 were RSV-seronaive at baseline. Most solicited and unsolicited adverse events after ChAd155-RSV occurred at similar or lower rates than after active comparators. In infants who developed RSV infection, there was no evidence of vaccine-associated enhanced respiratory disease (VAERD). RSV-A neutralizing titers and RSV F-binding antibody concentrations were higher post-ChAd155-RSV than postcomparator at days 31, 61, and end of RSV season 1 (mean follow-up, 7 months). High-dose ChAd155-RSV induced stronger responses than low-dose, with further increases post-dose 2. Conclusions. ChAd155-RSV administered to 6- to 7-month-olds had a reactogenicity/safety profile like other childhood vaccines, showed no evidence of VAERD, and induced a humoral immune response.

BACKGROUND:A multicomponent meningococcal serogroups ABCWY vaccine (MenABCWY) could provide broad protection against disease-causing meningococcal strains and simplify the immunisation schedule. The aim of this trial was to confirm the effect of the licensed meningococcal serogroup B (MenB) vaccine, 4CMenB, against diverse MenB strains, and to assess the breadth of immune response against a panel of 110 MenB strains for MenABCWY containing the antigenic components of 4CMenB and licensed serogroups ACWY vaccine, MenACWY-CRM, the non-inferiority of the immune response with MenABCWY versus 4CMenB and MenACWY-CRM, safety, and MenABCWY lot-to-lot consistency. METHODS:We conducted a phase 3 randomised, controlled, observer-blinded trial of healthy adolescents and young adults (age 10-25 years) across 114 centres in Australia, Canada, Czechia, Estonia, Finland, Türkiye, and the USA. Exclusion criteria included previous vaccination with a MenB vaccine or (within the last 4 years) MenACWY vaccine. Participants were randomly allocated (5:5:3:3:3:1 ratio) via a central randomisation system using a minimisation procedure to receive 4CMenB at months 0, 2, and 6 (referred to as 4CMenB 0-2-6 hereafter); or 4CMenB at months 0 and 6 (referred to as 4CMenB 0-6 hereafter); or MenABCWY (three groups, each receiving one production lot of the MenACWY-CRM component) at months 0 and 6; or MenACWY-CRM at month 0. Demonstration in the per-protocol set of the consistency of three MenACWY-CRM component lots of the MenABCWY vaccine was a primary objective (demonstrated with two-sided 95% CIs for the ratio of human serum bactericidal antibody [hSBA] geometric mean titres against each serogroup within predefined criteria [0·5-2·0]). The primary endpoints (breadth of immune response) for the MenB component of MenABCWY and 4CMenB were measured using the endogenous complement hSBA (enc-hSBA) assay against a panel of 110 diverse MenB invasive disease strains. For each serum sample, 35 strains from the 110 MenB strain panel were randomly selected for testing. The 4CMenB breadth of immune response data have been published separately. For MenABCWY, breadth of immune response was assessed in two analyses: a test-based analysis of the percentage of samples (tests) without bactericidal serum activity against MenB strains 1 month after two MenABCWY doses versus the percentage after one MenACWY-CRM dose in the per-protocol set, and a responder-based analysis of the percentage of participants (responders) whose sera killed 70% or more strains at 1 month after two MenABCWY doses in the full analysis set. A lower limit of two-sided 95% CI above 65% would demonstrate breadth of immune response. Other primary outcomes included non-inferiority (5% margin) of two MenABCWY doses versus two 4CMenB doses by enc-hSBA assay in the per-protocol set, non-inferiority (10% margin) of two MenABCWY doses versus one MenACWY-CRM dose in MenACWY vaccine-naive participants by traditional hSBA assay in the per-protocol set, and safety in all vaccinated participants. This trial is registered with ClinicalTrials.gov, NCT04502693, and is complete. FINDINGS:Between Aug 14, 2020, and Sept 3, 2021, 3651 participants were enrolled and randomly allocated (900 in the 4CMenB 0-2-6 group and 908 in the 4CMenB 0-6 group, 1666 in the three MenABCWY groups combined, and 177 in the MenACWY-CRM group). All primary objectives for MenABCWY were met. Consistency of immune responses against the three production lots of the MenACWY component of MenABCWY was demonstrated since two-sided 95% CIs for the ratios of hSBA geometric mean titres against serogroups A, C, W, and Y for each pair of lots were within the predefined equivalence criteria. The lot data were pooled for the remainder of MenABCWY endpoints. By enc-hSBA assay, breadth of immune response against the MenB strain panel was 77·9% (95% CI 76·6 to 79·2) in the test-based analysis and 84·1% (81·4 to 86·5; 687 of 817 participants) in the responder-based analysis. Non-inferiority of MenABCWY to 4CMenB was demonstrated by enc-hSBA assay: the difference in percentage of samples with bactericidal serum activity between the MenABCWY group (82·5% [95% CI 82·1 to 83·0]; 21 222 of 25 715) and 4CMenB 0-2 group (83·1% [82·7 to 83·6]; 22 921 of 27 569) was -0·61% (-1·25 to 0·03). Non-inferiority of two-dose MenABCWY to one-dose MenACWY-CRM was demonstrated by traditional hSBA assay, with differences between the MenABCWY group and MenACWY group in percentages of participants with a four-fold rise in hSBA titres of 11·3% (5·9 to 19·0) for serogroup A, 47·2% (38·1 to 56·3) for serogroup C, 35·3% (26·9 to 44·5) for serogroup W, and 27·0% (19·4 to 35·8) for serogroup Y. MenABCWY reactogenicity was mostly of mild or moderate severity and transient, with similar frequencies of adverse events in the MenABCWY and 4CMenB groups and no safety concerns were identified. INTERPRETATION:This study demonstrates breadth of immune response against a panel of 110 MenB strains for the MenB component of the investigational MenABCWY vaccine, when administered as a 0-6 months schedule to the target population of adolescents and young adults, with predefined criteria for success met for both breadth of immune response endpoints and for non-inferiority versus 4CMenB. This investigational vaccine could provide broad meningococcal serogroup coverage in a simplified immunisation schedule, thus aiding the public health attempt in preventing invasive meningococcal disease due to five Neisseria meningitidis serogroups in adolescents and young adults. FUNDING:GSK.

BACKGROUND:Varicella vaccine, a live-attenuated Oka-strain of varicella zoster virus (VZV), is a recommended childhood vaccine by many countries. As with wild varicella strain, after primary infection, the live-attenuated virus can establish latency in sensory ganglia and reactivate causing vaccine-strain illnesses: herpes zoster (HZ), visceral or peripheral and central nervous system dissemination. We report a case of early reactivation of live-attenuated virus-HZ and meningoencephalitis-in an immunocompromised child. METHODS:This is a retrospective descriptive report of a case, in a tertiary pediatric hospital, CHU Sainte-Justine (Montréal, Canada). RESULTS:An 18 month-year old girl diagnosed with a primitive neuro-ectodermal tumor (PNET) received the day prior to diagnosis, a first varicella vaccine (MMRV). She received chemotherapy 20 days post MMRV vaccine and autologous bone marrow transplantation 3 months post vaccination. She was considered not eligible, to acyclovir prophylaxis prior transplantation (positive for VZV IgG and negative for herpes simplex virus IgG by ELISA). At day 1 post transplantation, she developed dermatomal HZ and meningoencephalitis. Oka-strain varicella was isolated, she was treated with acyclovir and foscarnet. Neurologic status improved in 5 days. Control of VZV viral load in cerebrospinal fluid showed a slow decrease to from 5.24 log 10 copies/mL to 2.14 log 10 copies/mL in 6 weeks. No relapse was observed. She recovered without neurological sequelae. CONCLUSIONS:Our experience highlights the importance of conducting a thorough medical history regarding vaccination and serological status of newly immunocompromised patients. Intensive chemotherapy succeeding live vaccine administration <4 weeks could have influenced early and severe viral reactivation. Early initiation of prophylactic antiviral treatment is questioned in such circumstances.

hDepartment of Microbiology, Infectious Diseases and Immunology, University of Montreal, Quebec, Canada Summary Background Respiratory viruses have been previously suspected to trigger invasive pneumococcal disease (IPD). After progressive non-pharmaceutical interventions (NPI) lifting, an unusual RSV outbreak has been observed in the Fall 2021, raising concerns about the possible consequences on IPD. We aimed to analyse the evolution of IPD incidence across age-groups since NPI lifting, and its temporal association with respiratory viral infections. Methods We conducted a time-series analysis using 1) population-based IPD surveillance data and 2) statistics from the laboratory surveillance network of respiratory viruses in the province of Quebec, Canada, from January 2013 to January 2022. The monthly IPD incidence was analysed by quasi-Poisson regression models across age-groups. The fraction of IPD incidence change potentially attributable to different viruses in 2021-2022 was estimated. Findings A total of 7712 IPD cases were included. After a major decrease in IPD incidence from April 2020, IPD rate started to increase in <5-year-old children in October 2021, exceeding the pre-NPI trend (+62%). This was temporally associated with an unusual surge in RSV cases (+53% versus pre-NPI trend). During this 2021-22 surge, the fraction of IPD attributable to RSV dynamics in children was 77% (95% CI [33-100]). By contrast, the IPD incidence in older age-groups remained low, and was temporally associated with influenza dynamics. Interpretation These results provide new evidence on the role of respiratory viruses in driving IPD dynamics, with possible differences between children and adults. In the coming future, the potential benefit of interventions tar -geting RSV, such as vaccines, for IPD prevention should be considered. Funding The study was supported by a grant from the Quebec Ministry of Health and Social Services ('ministere de la Sante et des Services sociaux du Quebec'). Publication was supported by a grant from "Fondation de l'Assistance Publique -Hopitaux de Paris et de l'Alliance << Tous Unis contre le Virus >> (Fondation de France/Institut Pasteur/ APHP)". N.O. was supported by the ESPID (European Society of Pediatric Infectious Diseases) 2021-2023 Fellowship Award and the 2022 ISPPD (International Symposium on Pneumococci and Pneumococcal Diseases) Robert Austrian Research award.

In the province of Quebec, Canada, a 2 + 1 dose pneumococcal conjugate vaccine (PCV) program for children was implemented in 2004. PCV7 was replaced by PCV10 in 2009, by PCV13 in 2011 and by PCV10 in 2018, without catch-up in all instances. The objective was to estimate PCV13 effectiveness to prevent serotype 3 invasive pneumococcal disease in children aged less than 5 years, using 2010-2018 mandatory notification and laboratory surveillance data, an indirect cohort design and multivariate logistic regression models. A total of 29 cases of serotype 3 and 290 non-vaccine serotype cases as controls were analysed. Overall vaccine effectiveness (& GE;1 dose) was estimated at 59% [-39% to 88%]. During the first year after the last dose effectivness was 88% [47% to 97%] whereas no protection was observed thereafter. There was no trend towards increased effectiveness with the number of doses. PCV13 protection against serotype 3 IPD seems to be short-lived.

Background In Canada, vaccination against pertussis (Tdap) during pregnancy has been recommended since 2018, with suboptimal uptake. We aimed to assess the determinants of intention and uptake of Tdap vaccine among pregnant women in Quebec. Methods Participants (< 21 weeks of pregnancy) were recruited in four Quebec regions. Two online surveys were administered during pregnancy (< 21 weeks and > 35 weeks). One measured vaccination intention and the other assessed the actual decision. Questionnaires were informed by the Theory of Planned Behaviour (TPB). We used logistic multivariate analysis to identify determinants of Tdap vaccination uptake during pregnancy using responses to both questionnaires. Results A total of 741 women answered the first survey and 568 (76.7%), the second survey. In the first survey most participants intended to receive the Tdap vaccine during their pregnancy (76.3%) and in the second survey, 82.4% reported having been vaccinated against Tdap during their pregnancy. In multivariate analysis, the main determinants of vaccine uptake were: a recommendation from a healthcare provider (OR = 7.6), vaccine intention (OR = 6.12), social norms (or thinking that most pregnant women will be vaccinated (OR = 3.81), recruitment site (OR = 3.61 for General Family Medicine unit) perceived behavioral control (or low perceived barriers to access vaccination services, (OR = 2.32) and anticipated feeling of guilt if not vaccinated (OR = 2.13). Safety concerns were the main reason for not intending or not receiving the vaccine during pregnancy. Conclusion We observed high vaccine acceptance and uptake of pertussis vaccine in pregnancy. The core components of the TPB (intention, social norms and perceived behavioral control) were all predictors of vaccine uptake, but our multivariate analysis also showed that other determinants were influential: being sufficiently informed about Tdap vaccination, not having vaccine safety concerns, and anticipated regret if unvaccinated. To ensure high vaccine acceptance and uptake in pregnancy, strong recommendations by trusted healthcare providers and ease of access to vaccination services remain instrumental.

OBJECTIVES:Individuals and healthcare providers may be uncertain about the safety of revaccination after an adverse event following immunization (AEFI). We identified factors associated with physician recommendation for revaccination and participant intention to be revaccinated among patients with adverse events following immunization (AEFIs) assessed in the Canadian Special Immunization Clinic (SIC) Network from 2013 to 2019.METHODS:This prospective observational study included patients assessed in the Canadian Special Immunization Clinic Network from 2013 to 2019 for an AEFI who required additional doses of the vaccine temporally associated with their AEFI. Participants underwent standardized assessment and data collection. Physician recommendations regarding revaccination and participant intent for revaccination were recorded. AEFI impact on daily activities and need for medical attention was captured as low, moderate, high impact and serious (e.g., requiring hospitalization). Multivariable logistic regression analysis identified factors associated with physician recommendation and participant intention for revaccination, controlling for province of assessment.RESULTS:Physician recommendation was significantly associated with the type of AEFI and AEFI impact. Compared to large local reaction, physician recommendation for revaccination was reduced for immediate hypersensitivity (aOR: 0.24 [95% CI: 0.08-0.76]) and new onset autoimmune disease (aOR: 0.16; 95% CI: 0.04-0.69). Compared to low impact AEFIs, physician recommendation was reduced for moderate (aOR: 0.22 [95% CI: 0.07-0.65]), high impact (aOR: 0.08 [95% CI: 0.02-0.30]), and serious AEFIs (aOR: 0.11 [95% CI: 0.03-0.37]). Participant intention for revaccination was significantly associated with AEFI impact, with reduced odds for high versus low impact AEFIs (aOR: 0.12 [95% CI: 0.04-0.42]).CONCLUSION:Physicians appear to use AEFI type and impact to guide recommendations while patients use primarily AEFI impact to form intentions for revaccination. The findings may help inform counselling for patients with AEFIs.