Audenz™ Avian Influenza H5N1 (Bird Flu) Vaccine Clinical Trials, Dosage, Efficacy, Indication, Side Effects
CSL Seqirus Inc. Audenz™ (aH5N1c) (STN: 125692) is a monovalent, adjuvanted, cell-based inactivated subunit vaccine designed to protect people from disease caused by the influenza A virus H5N1 subtype in the event of avian influenza pandemics. During H5N1 bird flu pandemics, a lack of preexisting immunity to novel influenza strains increases morbidity and mortality. Audenz is a milky-white sterile injectable emulsion prepared from a virus propagated in Madin Darby Canine Kidney cells for intramuscular use.
AudAudenz'sitial U.S. Food and Drug Administration (FDA) Approval was in January 2020 for use in persons six months and older, and it received Supplemental FDA approval in 2021. Clinical safety data for AUDENZ in adults have been collected from three studies: Study 1 in adults 18 through 64 years of age (NCT01776541); Study 2 in adults 65 years of age and older (NCT01766921), and Study 3, a placebo-controlled trial in adults 18 years of age and older (NCT02839330). Subjects in all studies received two doses of AUDENZ, administered intramuscularly 21 days apart. Limited adverse events were detected.
CSL Seqirus has produced zoonotic vaccines to address the H5N1 threat using egg-based technology at its Liverpool, UK facility (virus grown in eggs) and cell-based technology at its Holly Springs, NC facility (virus grown in cells). The Holly Springs, NC, facility was built through a public-private partnership established in 2009 with BARDA. It is the world's largest cell-based influenza vaccine producer and the first such domestic facility.
Both technologies utilize CSL Seqirus' MF59®-adjuvanted technology and have been proven capable of producing vaccines against various strains of pandemic potential. The current egg-based adjuvanted zoonotic vaccine is produced based on the approved Aflunov platform, while the cell-based adjuvanted zoonotic vaccine is produced based on the approved Audenz platform.
The journal Vaccines confirmed on December 11, 2021, four studies (total N = 6,230) 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). 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.
On March 23, 2022, a peer-reviewed study published by the journal Vaccines reported that 'A cell-based process' may be better suited for vaccine production during an HPAI pandemic; the aH5N1c influenza vaccine (Audenz) elicited high levels of antibodies following two vaccinations administered 21 days apart and met immunogenicity criteria at Day 43 among both younger and older adults with a clinically acceptable safety profile. The consistency of the three consecutive aH5N1c vaccine lots was demonstrated in a phase 3 study.
Seqirus has a five-year agreement with the Biomedical Advanced Research and Development Authority (BARDA), a division of the Assistant Secretary for Preparedness and Response Office (ASPR) within the U.S. Department of Health and Human Services, to supply products. Avian influenza vaccines ensure that people can be vaccinated as directed by the U.S. National Influenza Vaccine Modernization Strategy and the American Pandemic Preparedness Plan. On June 2, 2022, the U.S. government confirmed that Seqirus has established and will maintain the required pandemic readiness to deliver 150 million doses of a cell-based pandemic influenza vaccine within six months of an influenza pandemic declaration in the U.S. During a bird-flu pandemic in the U.S., BARDA would source vaccines from the CSL Seqirus Holly Springs, NC facility in a pandemic. BARDA certified this facility in June 2022. The product is not marketed directly to consumers or available through traditional retail channels.
An alternative to traditional egg-based manufacturing, cell-based manufacturing avoids egg-adapted changes, one source of strain mismatch between the vaccine and circulating pandemic influenza virus. The antigen is stockpiled and, in the event of an influenza A (H5N1) pandemic, would be rapidly formulated into doses for the U.S. government. Audenz combines Seqirus's proprietary MF59® adjuvant technology with its cell-based manufacturing platform. Access to pre-pandemic vaccines using either cell- or egg-based manufacturing technologies from SeqSeqirus'sobal production facilities, including Holly Springs, North Carolina; Liverpool, United Kingdom; and Parkville, Australia.
As of July 2024, the U.S. Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) consider the current risk to the general public from the ongoing H5N1 outbreak in wild birds, poultry, and mammals to be low. Accordingly, the CDC published an updated Avian Influenza Current Situation Summary in June 2024. The WHO published on April 19, 2023, The Pandemic Influenza Pandemic FraFramework 'srtnership Contribution High-Level Implementation Plan III, outlines the strategy for strengthening global pandemic influenza preparedness from 2024 to 2030.
U.S. FDA STN: 125692; BLA Approval; Supplemental Approval Letter: BL125692/18; Package Insert. There is no postmarketing experience following the administration of AUDENZ, and no data are available to evaluate the concomitant administration of AUDENZ with other vaccines. There is insufficient data on AUDENZ in pregnant women to inform vaccine-associated risks in pregnancy.
New Jersey-based CSL Seqirus is a global leader in influenza prevention (ASX: CSL). Its trademark is 88789443.
Audenz Vaccine Indication
Audenz is indicated to protect individuals six months of age and older against influenza A(H5N1) in a pandemic. Do not administer AUDENZ to anyone with a history of a severe allergic reaction (e.g., anaphylaxis) to any vaccine component or after a previous dose of an influenza vaccine.
Audenz Vaccine Dosage
Audenz is administered as an intramuscular injection. It is given in two doses, .5 ml each, 21 days apart. The U.S. FDA approved a multi-dose vial presentation for Audenz on November 23, 2021.
Audenz Vaccine Immunocompromised
Immunocompromised persons, including those receiving immunosuppressive therapy, may have a diminished immune response to AUDENZ.
Audenz Vaccine Side Effects
In adults 18 through 64 years of age, the most common (≥ 10%) solicited local and systemic reactions reported in clinical trials were injection site pain (64%), fatigue (25%), and headache (25%). Avoid use if there is any history of a severe allergic reaction (e.g., anaphylaxis) to any vaccine component or after a previous dose of an influenza vaccine. To report SUSPECTED ADVERSE REACTIONS, contact Seqirus at 1855358, VAERSAERS at 1800822,7,967, or www.vaers.hhs.gov.
Audenz Vaccine Serious Adverse Events
In Clinical Study 3, the FDA disclosed fatal and non-fatal SAEs reported in the 12 months following vaccinations among adults 18 through 64 years of age occurred in 2.9% of subjects who received AUDENZ and 3.3% of subjects who received placebo. SAE rates among adults 65 and older were 10.5% in subjects administered AUDENZ and 15.3% in subjects who received a placebo. Fatal SAEs included 11 (0.5%) AUDENZ recipients and 1 (0.1%) placebo recipients. No SAEs were assessed as being related to AUDENZ. Studies 1 and 2 did not have a placebo or active comparator control for safety comparison. Four deaths occurred in Study 1 (subjects 18 through 64 years) and two in Study 2 (subjects ≥ 65 years), none assessed as related to AUDENZ. In the 12 months following vaccinations, SAEs (fatal and non-fatal) occurred in n=28 (3%) of all subjects in Study 1. SAEs occurred in a total of n=96 (7%).
Pandemic Influenza Vaccines
Pandemic influenza occurs when a new flu virus emerges for which humans have little or no immunity, allowing the virus to spread rapidly from person to person worldwide. Under the terms of an agreement in May 2024, CSL Seqirus will deliver approximately 4.8 million doses of pre-pandemic vaccine matched to the H5 of the currently circulating H5N1 strain. This is the fourth award CSL Seqirus has received from BARDA.
Audenz Vaccine News
October 4, 2024 - “Pandemic preparedness is a core part of who we are,” said Jon Kegerise, Vice President of Manufacturing and Site Head at CSL Seqirus Holly Springs. "Our Holly Springs site was built to deliver innovative pandemic solutions at industrial scale and speed."
May 16, 2024 - Do We Have Enough Bird Flu Vaccines for a Potential Pandemic?
June 14, 2023 - The U.S. CDC published H5N1 Bird Flu: Current Situation Summary.
April 14, 2023—The United States Department of Agriculture's Agricultural Research Service researchers are testing several vaccine candidates. Initial data from the animal study with a single dose of the vaccine are expected to be available in May 2023. The researchers expect two-dose vaccine challenge studies with results in June 2023.
December 21, 2022 - The UKHSA published an original Research and Analysis investigation into the risk to human health of avian influenza (influenza A H5N1) in England: technical briefing #1.
July 29, 2022 - "It is best practice never to touch or handle deceased birds or exhibit signs of distress or illness," says Dr. Sundari Mase, Sonoma County health officer. "While severe cases of bird flu are possible in humans, we rarely see symptoms develop beyond those of the common cold."
J"ne 2, 2022 - CSL Seqirus announced its facility in Holly Springs, North Carolina. As the Biomedical Advanced Research and Development Authority outlined, it has successfully achieved all criteria required to establish domestic manufacturing capability for cell-based seasonal and pandemic influenza vaccines.
May 26, 2022 - The journal Nature published: Why unprecedented bird flu outbreaks sweep the world concern scientists.
May 17, 2022 - The U.S. CDC recently added the Eurasian H5N1 avian flu strain to the list of animal flu viruses with zoonotic potential.
April —2022 - The United States Department of AgrAgriculture'simal and Plant Health Inspection Service confirmed the presence of HPAI in a commercial pheasant flock in Erath County, Texas, thstate state, to confirm a HAPI outbreak in 2022.
February 25, 2022 - Seqirus announced the renewal of a five-year agreement with the BARDA, a division of the Office of the Assistant Secretary for Preparedness and Response. This agreement empowers BARDA to request that Seqirus provide influenza vaccines and adjuvants for pre-pandemic stockpiling or manufacture to support rapid response to an influenza pandemic or other public health emergency. Seqirus and BARDA have held similar agreements since 2006.
November 23, 2021—The FDA has approved AUDENZ's multi-dose vial presentation to help protect individuals six months of age and older against influenza A(H5N1) in a pandemic.
October 4, 2021 - Seqirus announced that the Biomedical Advanced Research and Development Authority selected Seqirus to develop two influenza A(H2Nx) vaccine candidates for assessment in Phase 1 clinical study to help safeguard communities in the event of an influenza pandemic. The first candidate will utilize cell-based and adjuvanted technologies, building on SeqSeqirus'sghly flexible combination platform technology used by AUDENZ.
February 3, 2020 - Seqirus Announces U.S. FDA Approval of Its First-Ever Adjuvanted, Cell-Based Pandemic Influenza A (H5N1) Vaccine.
January 31, 2020 - The FDA approves SeqSeqirus'ologics License Application for Influenza A (H5N1) Monovalent Vaccine, Adjuvanted effective for use in persons six months and older. For use in persons six months through 17 years of age, the FDA has approved the BLA according to the regulations for accelerated approval, 21 CFR 601.41.
Audenz Influenza A(H5N1) Vaccine Clinical Trials
Audenz has been studied in various clinical trials.
