Phase 3 Randomized, Multicenter, Placebo-Controlled Study to Evaluate Safety, Immunogenicity, and Lot-to-Lot Consistency of an Adjuvanted Cell Culture-Derived, H5N1 Subunit Influenza Virus Vaccine in Healthy Adult Subjects

A cell-based process may be better suited for vaccine production during a highly pathogenic avian influenza (HPAI) pandemic. This was a phase 3, randomized, controlled, observer-blind, multicenter study evaluated safety, immunogenicity, and lot-to-lot consistency of two doses of a MF59-adjuvanted, H5N1 influenza pandemic vaccine manufactured on a cell culture platform (aH5N1c) in 3196 healthy adult subjects, stratified into two age groups: 18 to <65 and ≥65 years. Immunogenicity was measured using hemagglutination inhibition (HI) titers. HI antibody responses increased after the first aH5N1c vaccine dose, and 3 weeks after the second vaccination (Day 43), age-appropriate US Center for Biologics Evaluation and Research (CBER) and former European Medicines Authority Committee for Medicinal Products for Human Use (EMA CHMP) immunogenicity criteria were met. Six months after the first vaccination, HI titers were above baseline but no longer met CBER and CHMP criteria. No relevant changes over time were seen in placebo subjects. Solicited AEs were more frequent in the active treatment than the placebo group, primarily due to injection site pain. No serious adverse events (SAEs) related to aH5N1c- were reported. aH5N1c influenza vaccine elicited high levels of antibodies following two vaccinations administered 21 days apart and met both CBER and former CHMP immunogenicity criteria at Day 43 among both younger and older adults with a clinically acceptable safety profile. Consistency of the three consecutive aH5N1c vaccine lots was demonstrated (NCT02839330)

Phase 3 Randomized, Multicenter, Placebo-Controlled Study to Evaluate Safety, Immunogenicity, and Lot-to-Lot Consistency of an Adjuvanted Cell Culture-Derived, H5N1 Subunit Influenza Virus Vaccine in Healthy Adult Subjects

A cell-based process may be better suited for vaccine production during a highly pathogenic avian influenza (HPAI) pandemic. This was a phase 3, randomized, controlled, observer-blind, multicenter study evaluated safety, immunogenicity, and lot-to-lot consistency of two doses of a MF59-adjuvanted, H5N1 influenza pandemic vaccine manufactured on a cell culture platform (aH5N1c) in 3196 healthy adult subjects, stratified into two age groups: 18 to &lt;65 and &ge;65 years. Immunogenicity was measured using hemagglutination inhibition (HI) titers. HI antibody responses increased after the first aH5N1c vaccine dose, and 3 weeks after the second vaccination (Day 43), age-appropriate US Center for Biologics Evaluation and Research (CBER) and former European Medicines Authority Committee for Medicinal Products for Human Use (EMA CHMP) immunogenicity criteria were met. Six months after the first vaccination, HI titers were above baseline but no longer met CBER and CHMP criteria. No relevant changes over time were seen in placebo subjects. Solicited AEs were more frequent in the active treatment than the placebo group, primarily due to injection site pain. No serious adverse events (SAEs) related to aH5N1c- were reported. aH5N1c influenza vaccine elicited high levels of antibodies following two vaccinations administered 21 days apart and met both CBER and former CHMP immunogenicity criteria at Day 43 among both younger and older adults with a clinically acceptable safety profile. Consistency of the three consecutive aH5N1c vaccine lots was demonstrated (NCT02839330)

Antibody responses against heterologous H5N1 strains for an MF59-adjuvanted cell culture–derived H5N1 (aH5n1c) influenza vaccine in adults and older adults

MF59-adjuvanted H5N1, cell culture-derived inactivated influenza vaccine (aH5N1c, AUDENZ®, Seqirus) is available for persons 6 months of age and older. During a pandemic, lack of preexisting immunity to novel influenza strains increases morbidity and mortality. This study examined the potential for an adjuvanted vaccine to provide cross-protection to novel viruses. Two similarly designed studies involving separate cohorts aged 18–64 and ≥65 y assessed immune responses to five heterologous H5N1 influenza strains elicited by two 7.5 μg doses of aH5N1c given 3 weeks apart. Geometric mean titers (GMT) on Days 1 and 43 and Day 43/Day 1 geometric mean ratios (GMRs) were determined with hemagglutination inhibition (HI) and microneutralization (MN). Rates of seroconversion (SC) and percentages of subjects with HI and MN ≥ 1:40 were determined. Significant increases in GMTs were observed on Day 43 after vaccination for all 5 heterologous strains in all ages tested. SC rates were 28–55% and 17–46% among those aged 18–64 and ≥65 y, respectively. MN ≥ 1:40 was observed in 38–100% of younger and 37–97% of older subjects, and HI ≥ 1:40 was achieved by 28–64% of subjects aged 18–64 y and by 17–57% of subjects aged ≥65 y. A SC rate ≥40% (97.5% CI) was met for two heterologous strains tested in adults aged 18–64 y. In adults aged 18–64 and ≥65 y, two 7.5 μg doses of aH5N1c demonstrated increased immunogenicity from baseline against five heterologous H5N1 strains, illustrating the potential for aH5N1c to provide cross-protection against other H5N1 strains

Analyses of Safety Profile and Homologous Antibody Responses to a Mammalian Cell-Based, MF59-Adjuvanted, A/H5N1, Pandemic Influenza Vaccine across Four Phase II/III Clinical Trials in Healthy Children, Adults, and Older Adults

Modern cell culture-based technology eliminates vaccine manufactures reliance on embryonated chicken eggs, which may become compromised during an avian influenza pandemic. Four studies (total N = 6230) assessed the immunogenicity and safety of mammalian cell-based, MF59®-adjuvanted, A/H5N1 vaccine (aH5N1c; AUDENZ™) as two doses administered on Days 1 and 22 in children (NCT01776554), adults (NCT01776541; NCT02839330), and older adults (NCT01766921; NCT02839330). Immunogenicity of formulations at 7.5 μg and 3.75 μg antigen per dose were assessed by hemagglutination inhibition and microneutralization assays on Days 1, 22, 43, and 183 or 387. Solicited local and systemic adverse events (AEs) were recorded for 7 days after each vaccination. Unsolicited AEs were collected for 21 days after each vaccination, and serious and other selected AEs were recorded for one year. Antibody responses after two 7.5 μg doses met CBER licensure criteria in all age groups. Overall, an age-related response was evident, with the highest responses observed in children <3 years old. In children, antibody titers met seroconversion criteria 12 months after vaccination. MF59 allowed for antigen dose sparing. Solicited AEs were mild to moderate in nature, of short duration, and less frequent after the second dose than the first, demonstrating a favorable risk-benefit profile

Outcomes in Pregnant Persons Immunized with a Cell-Based Quadrivalent Inactivated Influenza Vaccine: A Prospective Observational Cohort Study

Objective: To evaluate pregnancy and infant outcomes among persons immunized with a cell-based quadrivalent inactivated influenza vaccine (IIV4c) during routine pregnancy care. Design: Prospective observational cohort. Setting: US-based obstetrics/gynecology clinics. Population: Pregnant persons. This US-based, prospective observational cohort study evaluated the safety of quadrivalent inactivated influenza vaccine (IIV4c; Flucelvax&reg; Quad) in pregnant persons immunized over 3 influenza seasons between 2017 and 2020. Pregnant persons were immunized with IIV4c as part of routine care, after which their health care provides HCPs with all observational data to a single coordinating center. Follow-up data were collected at the end of the second trimester and/or at the time of pregnancy outcome. A scientific advisory committee reviewed the data. Prevalence point estimates were reported with 95% confidence intervals (CIs). Pregnancy outcomes included: live birth, stillbirth, spontaneous abortion, elective termination, and maternal death. Infant outcomes included: preterm birth (&lt;37 weeks gestational age), low birth weight (&lt;2500 g), or major congenital malformations (MCMs). Of the 665 evaluable participants, 659 (99.1%) had a live birth. No stillbirths (0% [95% CI 0.0&ndash;0.6]), 4 spontaneous abortions (1.9% [0.5&ndash;4.8]), and 1 elective termination (0.5% [0.0&ndash;2.6]) were reported. Among 673 infants, 9.2% (upper 95% CI 11.5%) were born prematurely, 5.8% (upper 95% CI 7.6%) had low birth weight, and 1.9% (upper 95% CI 3.1%) were reported to have an MCM. No maternal deaths were reported. Of the 2 infants who died shortly after birth, one was adjudicated as not related to the vaccine; the other&rsquo;s cause could not be determined due to maternal loss to follow-up. The prevalence of adverse pregnancy outcomes or preterm birth, low birth weight, or MCMs in newborns was similar in persons vaccinated with IIV4c compared to the rates observed in US surveillance systems. The safety profile of IIV4c in pregnant persons is consistent with previously studied influenza vaccines

A Prospective Cohort Study on Pregnancy Outcomes of Persons Immunized with a Seasonal Quadrivalent Inactivated Influenza Vaccine during Pregnancy

This US-based, prospective observational cohort study evaluated the safety of a quadrivalent inactivated influenza vaccine (IIV4; Afluria Quadrivalent) in pregnant persons immunized over four influenza seasons between 2017 and 2021. Pregnancy outcomes included live birth, stillbirth, spontaneous abortion, and elective termination. Infant events of interest were major congenital malformations (MCMs), preterm birth (&lt;37 weeks gestational age), and low birth weight (LBW). Data were descriptive; prevalence point estimates were reported with 95% confidence intervals (CI). A total of 483 pregnant persons were given IIV4 and evaluated; 477 (98.8%) reported a live birth, and there were 2 stillbirths, 4 spontaneous abortions, and no elective terminations or maternal deaths. The prevalence rates of infant events were as follows: preterm birth, 7.2% (upper 95% CI, 9.6%); LBW, 5.4% (upper 95% CI, 7.4%); and MCMs, 0.8% (upper 95% CI, 1.9%). Point estimates and upper 95% CIs of the observed prevalence rates were lower than or similar to background prevalence in the general US population. Our findings suggest no evidence of a safety concern with vaccinating this group at high risk of influenza complications and are consistent with published data from databases and surveillance systems that monitor the safety of influenza vaccines in pregnant persons

Outcomes of Staphylococcus aureus Infection in Hemodialysis-Dependent Patients

Background and objectives: Staphylococcus aureus is a leading cause of infection in patients with ESRD. Clinical and economic outcomes associated with S. aureus bacteremia and other S. aureus infections in patients with ESRD were examined