High-Dose Quadrivalent Influenza Vaccine for Prevention of Cardiovascular and Respiratory Hospitalizations in Older Adults.

BACKGROUND: We assessed the relative vaccine effectiveness (rVE) of high-dose quadrivalent influenza vaccine (QIV-HD) versus standard-dose quadrivalent influenza vaccine (QIV-SD) in preventing respiratory or cardiovascular hospitalizations in older adults. METHODS: FinFluHD was a phase 3b/4 modified double-blind, randomized pragmatic trial. Enrolment of 121,000 adults ≥65 years was planned over three influenza seasons (October to December 2019-2021). Participants received a single injection of QIV-HD or QIV-SD. The primary endpoint was first occurrence of an unscheduled acute respiratory or cardiovascular hospitalization (ICD-10 primary discharge J/I codes), from ≥14 days post-vaccination until May 31. The study was terminated after one season due to COVID-19; follow-up data for 2019-2020 are presented. RESULTS: 33,093 participants were vaccinated (QIV-HD, n = 16,549; QIV-SD, n = 16,544); 529 respiratory or cardiovascular hospitalizations (QIV-HD, n = 257; QIV-SD, n = 272) were recorded. The rVE of QIV-HD versus QIV-SD to prevent respiratory/cardiovascular hospitalizations was 5.5% (95% CI, -12.4 to 20.7). When prevention of respiratory and cardiovascular hospitalizations were considered separately, rVE estimates of QIV-HD versus QIV-SD were 5.4% (95% CI, -28.0 to 30.1) and 7.1% (95% CI, -15.0 to 25.0), respectively. Serious adverse reactions were <0.01% in both groups. CONCLUSIONS: Despite insufficient statistical power due to the impact of COVID-19, rVE point estimates demonstrated a trend toward a benefit of QIV-HD over QIV-SD. QIV-HD was associated with lower respiratory or cardiovascular hospitalization rates than QIV-SD, with a comparable safety profile. Adequately powered studies conducted over multiple influenza seasons are needed to determine statistical significance of QIV-HD compared with QIV-SD against preventing respiratory and cardiovascular hospitalizations. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT04137887.

Structured Benefit-Risk Assessment of a New Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) in Individuals Ages 12 Months and Older.

INTRODUCTION: A favorable benefit-risk balance is required to support licensure of biologics, in keeping with regulatory agencies' evolving recommendations, including the United States Food and Drugs Administration. We present a structured semi-quantitative benefit-risk analysis of MenACYW-TT, a quadrivalent meningococcal conjugate vaccine against Neisseria meningitidis serogroups, A, C, W and Y versus licensed comparators in individuals aged ≥ 12 months. METHODS: We used data from six MenACYW-TT clinical trials, stratified by age group, versus licensed vaccines: toddlers (12-23 months; Nimenrix® [MCV4-TT]), children (2-9 years; Menveo® [MCV4-CRM]), adolescents (10-17 years; MCV4-CRM or Menactra® [MCV4-DT]), adults (18-55 years; MCV4-DT) and older adults (≥ 56 years; Menomune®-A/C/Y/W-135 [MPSV4]). Eight benefit (seroresponse and seroprotection for A, C, W and Y) and five risk outcomes (any and grade 3 solicited injection site and systemic reactions, and serious adverse events) were measured at Day 30 after initial vaccination. Analyses were conducted by baseline vaccination status (meningococcal vaccine-naïve or vaccine-primed). RESULTS: MenACYW-TT showed favorable seroresponse and seroprotection among vaccine-naïve participants aged ≥ 2 years, against all serogroups, compared with MCV4-CRM, MCV4-DT and MPSV4. In vaccine-naïve toddlers, there was a favorable effect for serogroup C, but no difference between MenACYW-TT and MCV4-TT for serogroups A, Y and W. A favorable effect for MenACYW-TT against serogroup C was observed in all vaccine-naïve and combined vaccine-naïve and MenC conjugate vaccine-primed groups. For all risk criteria, there were no differences between MenACYW-TT and MCV4s in toddlers, children, adolescents and adults. Results for solicited injection site and systemic reactions favored MPSV4 in older adults. CONCLUSIONS: The benefit-risk profile for MenACYW-TT showed favorable seroresponse and seroprotection in individuals aged ≥ 2 years and no difference in risk criteria between MenACYW-TT and MCV4s. MenACYW-TT may provide an alternative to the standard-of-care for meningococcal disease prevention in those aged ≥ 12 months.

Safety of recombinant quadrivalent influenza vaccine compared to inactivated influenza vaccine in Chinese adults: An observational study.

BACKGROUND: Recombinant influenza vaccine (RIV) has been in use in US adults since 2013. This study evaluated the safety of quadrivalent recombinant influenza vaccine (RIV4, Flublok® Quadrivalent, Sanofi Pasteur) compared with standard-dose quadrivalent inactivated influenza vaccine (SD-IIV4) in self-identified Chinese adults at Kaiser Permanente Northern California (KPNC). METHODS: This study evaluated adults aged 18-64 years within KPNC during the 2018-2019 influenza season who self-identified as Chinese (NCT03694392). We compared the rates of prespecified diagnoses of interest in the emergency department and inpatient settings as done in prior influenza studies, for three risk intervals: 0-2 days, 0-13 days, and 0-41 days following influenza vaccination, as well as number of deaths within 0-180 days after vaccination. We estimated the odds ratios (ORs) and 95% confidence intervals using logistic regression adjusted for sex, age group, presence of comorbidities, and same-day concomitant vaccination. RESULTS: Comparing 15,574 adults who received RIV4 with 27,110 who received SD-IIV4, there was no statistically significant difference in the prespecified diagnoses of interest and deaths between the 2 groups. There were 35 deaths total, none of which were considered to be related to influenza vaccination. CONCLUSIONS: This study did not identify any safety concerns regarding RIV4 use among 18-64-year-olds who self-identified as Chinese. This study supports the safety of RIV4 vaccine in this population.

Exposure to quadrivalent influenza vaccine during pregnancy: Results from a global pregnancy registry.

BACKGROUND: The Fluzone® Quadrivalent (IIV4, Sanofi Pasteur) Pregnancy Registry was created to monitor vaccine safety during pregnancy (clinicaltrials.gov, NCT01945424). Here, we describe maternal, pregnancy, obstetrical and neonatal outcomes after vaccine exposure in pregnant women between August 2013 and September 2019. METHODS: All women exposed to IIV4 during their pregnancy were eligible for inclusion. Outcomes were prospective (reported following vaccine exposure but before knowledge of pregnancy outcome ascertained through prenatal tests) or retrospective (prenatal tests were undertaken before the exposure was reported). RESULTS: Among 239 IIV4 vaccine exposure reports received, there were 105 prospective and 10 retrospective reports of maternal adverse events (AEs). The most frequent prospectively reported maternal AEs were medication errors (expired product [n = 8, 3.8%]; extra dose [n = 7, 3.3%]) and injection site pain (n = 7, 3.3%). Among 62 prospectively reported pregnancy and obstetrical events with available follow-up information, seven AEs were reported, four (6.4%) of which were spontaneous abortions. A further seven AEs were reported among the 29 retrospective pregnancy and obstetrical events with available follow-up information. Among neonatal outcomes (15 prospective; 28 retrospective), >85% were reported as full-term births. One premature birth was reported prospectively. Four other neonatal AEs were reported, all retrospectively: two cases of talipes (club foot), one central nervous system anomaly and one atrial septal defect. All infants with available information had normal APGAR scores at 5 minutes. CONCLUSIONS: The frequency of AEs following exposure to IIV4 during pregnancy did not indicate new safety concerns.

Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) standardized template for collection of key information for benefit-risk assessment of live-attenuated viral vaccines.

Several live-attenuated viral vaccine candidates are among the COVID-19 vaccines in development. The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) has prepared a standardized template to describe the key considerations for the benefit-risk assessment of live-attenuated viral vaccines. This will help key stakeholders assess potential safety issues and understand the benefit-risk of such vaccines. The standardized and structured assessment provided by the template would also help to contribute to improved communication and support public acceptance of licensed live-attenuated viral vaccines.

The Brighton Collaboration standardized template for collection of key information for benefit-risk assessment of inactivated viral vaccines.

Inactivated viral vaccines have long been used in humans for diseases of global health threat and are now among the vaccines for COVID-19 under development. The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) has prepared a standardized template to describe the key considerations for the benefit-risk assessment of inactivated viral vaccines. This will help key stakeholders to assess potential safety issues and understand the benefit-risk of the vaccine platform. The standardized and structured assessment provided by the template would also help to contribute to improved communication and support public acceptance of licensed inactivated viral vaccines.

Preterm birth: Case definition & guidelines for data collection, analysis, and presentation of immunisation safety data.

Preterm birth is commonly defined as any birth before 37 weeks completed weeks of gestation. An estimated 15 million infants are born preterm globally, disproportionately affecting low and middle income countries (LMIC). It contributes directly to estimated one million neonatal deaths annually and is a significant contributor to childhood morbidity. However, in many clinical settings, the information available to calculate completed weeks of gestation varies widely. Accurate dating of the last menstrual period (LMP), as well as access to clinical and ultrasonographic evaluation are important components of gestational age assessment antenatally. This case definition assign levels of confidence to categorisation of births as preterm, utilising assessment modalities which may be available across different settings. These are designed to enable systematic safety evaluation of vaccine clinical trials and post-implementation programmes of immunisations in pregnancy.