Clinical trial and postmarketing safety experience with MenACWY-TT, a meningococcal group A, C, W, and Y tetanus conjugate vaccine.

Background: The meningococcal serogroups A, C, W, and Y tetanus toxoid conjugate vaccine (MenACWY-TT; Nimenrix®; Pfizer Ltd, Sandwich, Kent, UK) is licensed in more than 80 countries worldwide for the prevention of meningococcal disease caused by serogroups A, C, W, and Y in individuals throughout their lifespans. This report summarizes safety data from the MenACWY-TT clinical development program and postmarketing experience.

Methods: Within the clinical study program, reactogenicity data were based on 3 primary studies, including a large pooled analysis across multiple age groups, and long-term safety data were derived from 3 studies evaluating long-term antibody persistence.

Safety and immunogenicity of a primary series and booster dose of the meningococcal serogroup B-factor H binding protein vaccine (MenB-FHbp) in healthy children aged 1-9 years: two phase 2 randomised, controlled, observer-blinded studies.

Background: The meningococcal serogroup B-factor H binding protein vaccine (MenB-FHbp) is licensed for use in children aged 10 years or older for protection against invasive serogroup B meningococcal disease. Because young children are at increased risk of invasive meningococcal disease, MenB-FHbp clinical data in this population are needed.

Methods: We conducted two phase 2 randomised, controlled, observer-blinded studies including healthy toddlers (age 12-23 months) across 26 Australian, Czech, Finnish, and Polish centres, and older children (age 2-9 years) across 14 Finnish and Polish centres.

Safety data from the MenB-FHbp clinical development program in healthy individuals aged 10 years and older.

Background: The MenB-FHbp vaccine (Trumenba®) is licensed in various countries for the prevention of meningococcal serogroup B disease in individuals ≥ 10 years of age. The clinical development program included 11 completed trials where, in each trial, MenB-FHbp had an acceptable safety profile after a primary vaccination series was administered to individuals 10-65 years of age. However, the detection of potential rare events was limited because of individual clinical trial size.

Efficacy and Safety of COVID-19 Convalescent Plasma in Hospitalized Patients: A Randomized Clinical Trial.

Importance: There is clinical equipoise for COVID-19 convalescent plasma (CCP) use in patients hospitalized with COVID-19.

Objective: To determine the safety and efficacy of CCP compared with placebo in hospitalized patients with COVID-19 receiving noninvasive supplemental oxygen.

Design, Setting, And Participants: CONTAIN COVID-19, a randomized, double-blind, placebo-controlled trial of CCP in hospitalized adults with COVID-19, was conducted at 21 US hospitals from April 17, 2020, to March 15, 2021.

Sex, Age, and Race Effects on Immunogenicity of MenB-FHbp, A Bivalent Meningococcal B Vaccine: Pooled Evaluation of Clinical Trial Data.

Introduction: An extensive clinical development program showed that the meningococcal serogroup B-factor H binding protein (MenB-FHbp) vaccine affords protection against MenB disease for adolescents and adults. Data were pooled from multiple studies within the program to examine whether MenB-FHbp immunogenicity was influenced by sex, age, or race.

Methods: Immunogenicity was assessed in subjects from seven studies who received 120 µg MenB-FHbp (at 0, 2, 6 months) and had evaluated immune responses against four representative test strains via serum bactericidal assays using human complement (hSBAs).

Ten-Year Antibody Persistence and Booster Response to MenACWY-TT Vaccine After Primary Vaccination at 1-10 Years of Age.

This phase 3B, open-label, extension study (NCT01962207) evaluated long-term persistence of antibodies induced by the quadrivalent meningococcal vaccine conjugated to tetanus toxoid (MenACWY-TT) compared with the meningococcal serogroup C vaccine conjugated to CRM (MenC-CRM) and the quadrivalent meningococcal polysaccharide vaccine (MenACWY-PS) 6 to 10 y after primary vaccination in toddlers (aged 1-<2 y; MenACWY-TT and MenC-CRM) and children (aged 2-<11 y; MenACWY-TT and MenACWY-PS). Antibody responses against meningococcal serogroups A, C, W, and Y were assessed by serum bactericidal antibody assays using rabbit (rSBA) or human (hSBA) complement. A MenACWY-TT booster dose at Year 10 was given to all eligible subjects regardless of the primary vaccine received.

A phase 2b/3b MenACWY-TT study of long-term antibody persistence after primary vaccination and immunogenicity and safety of a booster dose in individuals aged 11 through 55 years.

Background: A previous phase 2 study demonstrated the immunogenicity of a single dose of meningococcal A, C, W, Y-tetanus toxoid conjugate (MenACWY-TT) or polysaccharide (MenACWY-PS) vaccine for up to 5 years in individuals aged 11-55 years. This follow-up study evaluated long-term antibody persistence up to 10 years and the immunogenicity and safety of a single MenACWY-TT booster dose given 10 years after primary vaccination.

Methods: Blood draws were conducted annually in Years 7-10.

Efficacy and safety of a booster dose of the meningococcal A, C, W, Y-tetanus toxoid conjugate vaccine administered 10 years after primary vaccination and long-term persistence of tetanus toxoid conjugate or polysaccharide vaccine.

A previous phase 3, randomized, multicenter study showed the immunogenicity of a primary vaccination of subjects aged 11 to 17 years with the quadrivalent meningococcal vaccine conjugated to tetanus toxoid (MenACWY-TT) or the quadrivalent meningococcal polysaccharide vaccine (MenACWY-PS). This extension study evaluated the safety and immunogenicity of a MenACWY-TT booster 10 years after receiving a primary dose of either MenACWY-TT or MenACWY-PS. The primary immunogenicity endpoint was booster response, evaluated using serum bactericidal antibody assays with rabbit complement (rSBA), 1 month postbooster.

Persistence of bactericidal antibodies following primary and booster MenACWY-TT vaccination of toddlers: A review of clinical studies.

The long-term persistence of antibody responses following primary vaccination with quadrivalent conjugate vaccines targeting meningococcal serogroups A, C, W, and Y (MenACWY) and the duration of protection following a booster dose have not been fully elucidated, particularly in children who received primary dosing as toddlers. This review summarizes the findings of one phase 3 and three phase 2 open-label, randomized clinical studies that assessed the long-term antibody persistence of MenACWY conjugated to tetanus toxoid as a carrier protein (MenACWY-TT) in toddlers. Following primary vaccination, antibody responses persisted for approximately 2-3 years and then decreased up to 5 years after vaccination.

Long-term antibody persistence after a booster dose of quadrivalent meningococcal ACWY-tetanus toxoid conjugate vaccine in healthy 5-year-old children.

Background: To provide continuing protection, available meningococcal vaccines must provide long-term persistence of circulating functional antibodies against prevalent serogroups causing invasive meningococcal disease (IMD). This study assessed antibody persistence and safety of the quadrivalent meningococcal vaccine conjugated to tetanus toxoid (MenACWY-TT) and the meningococcal serogroup C vaccine conjugated to Corynebacterium diphtheriae CRM protein (MenC-CRM) for up to 6 years after booster dosing in children.

Methods: In the primary vaccination study, children were vaccinated at age 12 to 23 months.

Immunogenicity and Safety of the 13-Valent Pneumococcal Conjugate Vaccine Administered in a 3 + 1 versus 2 + 1 Dose Schedule Among Infants in China.

Background: 13-valent pneumococcal conjugate vaccine (PCV13) was licensed in China based on immunologic noninferiority to 7-valent PCV (PCV7). As part of the noninferiority study, immunogenicity and safety of PCV13 administered as a 3- or 2-dose infant series followed by a toddler dose were examined in healthy Chinese infants.

Methods: Infants (42- to 77-days-old) were randomized to a 3-dose PCV13 or PCV7 infant series administered double-blind at 3, 4 and 5 months or PCV13 administered open-label at 2, 4 and 6 months and a 2-dose open-label series at 3 and 5 months; all subjects received a toddler dose (12 months).

Concomitant administration of meningococcal vaccines with other vaccines in adolescents and adults: a review of available evidence.

Invasive meningococcal disease (IMD), a rapidly progressing and potentially fatal illness, disproportionately affects adolescents and young adults. While IMD is best prevented by vaccination, vaccine uptake in these groups is low. An evidence-based understanding of the safety and effectiveness of concomitant vaccination of meningococcal vaccines, including the newer MenB protein vaccines and the more established MenACWY conjugate vaccines, with other vaccines recommended for adolescents and young adults may help maximize vaccination opportunities.

Persistence of antibodies 1 year after sequential administration of the 13-valent pneumococcal conjugate vaccine and the 23-valent pneumococcal polysaccharide vaccine in adults.

Vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) followed ≥ 1 year by the 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended for immunocompetent adults ≥ 65 years of age in the United States. This study assessed antipneumococcal opsonophagocytic activity (OPA) geometric mean titers (GMTs) to PCV13 in PPSV23-naive and PPSV23-preimmunized adults 1 year after a second vaccine dose. Two parent studies were conducted previously: (1) PPSV23 vaccine-naive subjects (60-64 years of age at enrollment) received PCV13 followed by PCV13 or PPSV23 1 year later or PPSV23 followed by PCV13 1 year later; and (2) subjects (≥ 70 years of age at enrollment) vaccinated with PPSV23 ≥ 5 years before study entry received PCV13 or PPSV23 followed by PCV13 1 year later.

The bivalent factor H binding protein meningococcal serogroup B vaccine elicits bactericidal antibodies against representative non-serogroup B meningococci.

MenB-FHbp (Trumenba®; bivalent rLP2086) is a meningococcal serogroup B vaccine containing 2 variants of the recombinant lipidated factor H binding protein (FHbp) antigen. The expression of FHbp, an outer membrane protein, is not restricted to serogroup B strains of Neisseria meningitidis (MenB). This study investigated whether antibodies elicited by MenB-FHbp vaccination also protect against non-MenB strains.

Meningococcal Group A, C, W, and Y Tetanus Toxoid Conjugate Vaccine: A Review of Clinical Data in Adolescents.

MenACWY-TT (Nimenrix) is a quadrivalent meningococcal vaccine containing polysaccharides from serogroups A, C, W, and Y conjugated to a tetanus toxoid carrier protein. MenACWY-TT is licensed in some countries as a three-dose primary series in individuals as young as 6 weeks of age and as a single dose in individuals ≥12 months of age. MenACWY-TT use is supported by long-term immunogenicity and safety across age groups, including data from several phase 2, 3, and 4 clinical studies in adolescents and young adults.

Clinical data supporting a 2-dose schedule of MenB-FHbp, a bivalent meningococcal serogroup B vaccine, in adolescents and young adults.

Invasive meningococcal disease (IMD) caused by Neisseria meningitidis is a potentially devastating condition that can result in death and is associated with serious long-term sequelae in survivors. Vaccination is the preferred preventative strategy. Quadrivalent polysaccharide-based vaccines that protect against infection caused by meningococcal serogroups A, C, W, and Y are not effective against meningococcal serogroup B (MenB), which was responsible for approximately 60% and 35% of confirmed IMD cases in the European Union and the United States in 2016, respectively.

Late onset of injection site reactions after vaccination with the 13-valent pneumococcal conjugate vaccine in adult study populations.

Injection site reactions (ISRs; redness, swelling and pain) commonly occur within 1-2 days after vaccination. After administration of toxoid vaccines including diphtheria toxoid, a later onset of ISRs has also been observed. As the serotype capsular polysaccharides in the 13-valent pneumococcal conjugate vaccine (PCV13) are conjugated to cross-reactive material 197 (CRM), a nontoxic variant of diphtheria toxin, the onset of ISRs over 14 days was explored in 8 adult studies with 19 cohorts.

Modeling excess zeroes in an integrated analysis of vaccine safety.

In prophylactic vaccine studies in healthy populations, many subjects do not experience a single adverse event (AE). Thus, the number of AEs observed in such clinical trials may be difficult to model because of an excess of zeroes relative to the parametric distributions assumed. To determine which type of modeling provides a better fit for observed AE data, a variety of models were applied to data from an integrated safety database from clinical trials of the meningococcal vaccine MenB-FHbp (Trumenba®, bivalent rLP2086; Pfizer Inc, Philadelphia, PA).

Serotype-specific immune responses to pneumococcal conjugate vaccine among children are significantly correlated by individual: Analysis of randomized controlled trial data.

Background: The magnitude of an individual's serotype-specific immunoglobulin G (IgG) response to a pneumococcal conjugate vaccine (PCV) has been associated with the vaccine's protective efficacy against carriage of pneumococci of that serotype, though the relationship with other serotypes needs to be understood.

Methods: Using immunogenicity data collected during a trial comparing the 7-valent (PCV7) and 13-valent (PCV13) vaccines, we measured associations between serotype-specific IgG levels, and used multiple regressions to identify demographic predictors of response.

Results: Vaccine-induced IgG levels were moderately positively correlated with one another, with pairwise correlation coefficients of 0.

A Bivalent Meningococcal B Vaccine in Adolescents and Young Adults.

Background: MenB-FHbp is a licensed meningococcal B vaccine targeting factor H-binding protein. Two phase 3 studies assessed the safety of the vaccine and its immunogenicity against diverse strains of group B meningococcus.

Methods: We randomly assigned 3596 adolescents (10 to 18 years of age) to receive MenB-FHbp or hepatitis A virus vaccine and saline and assigned 3304 young adults (18 to 25 years of age) to receive MenB-FHbp or saline at baseline, 2 months, and 6 months.

Brompheniramine and Chlorpheniramine Pharmacokinetics Following Single-Dose Oral Administration in Children Aged 2 to 17 Years.

Two pediatric studies characterized brompheniramine and chlorpheniramine pharmacokinetics in a total of 72 subjects, aged 2 to 17 years. A single age-/weight-based oral dose, ranging from 1 to 4 mg, was administered with 2 to 6 oz of water at least 2 hours after a light breakfast. Plasma samples were obtained before and for 72 hours after dosing and analyzed using high-pressure liquid chromatography-tandem mass spectrometry.

Safety and Immunogenicity of 13-Valent Pneumococcal Conjugate Vaccine in Children 6-17 Years of Age in India: An Open-label Trial.

In an open-label study in India, 200 healthy participants 6-17 years of age received 13-valent pneumococcal conjugate vaccine (PCV13). PCV13 elicited robust functional antibody immune responses. No adverse events were reported by caregivers at the 1-month follow-up visit.

Vaccine development to prevent Staphylococcus aureus surgical-site infections.

Background: Staphylococcus aureus surgical-site infections (SSIs) are a major cause of poor health outcomes, including mortality, across surgical specialties. Despite current advances as a result of preventive interventions, the disease burden of S. aureus SSI remains high, and increasing antibiotic resistance continues to be a concern.