Journal Article

Immunogenicity, safety, and lot consistency of the anthrax vaccine adsorbed, adjuvanted for post-exposure prophylaxis of anthrax in healthy adults: A phase 3, randomized, double-blind trial

Drobic, Bojan, Kim, Julia, Beach, Marinda, Komlenovic, Vanja, Akintunde, Gideon, Mirceta, Mila

2026

Overview

This double-blinded randomized Phase 3 study evaluated the immunogenicity and safety of CYFENDUS® vaccine (AV7909; Anthrax Vaccine Adsorbed, Adjuvanted) to support licensure for post-exposure prophylaxis following suspected or confirmed Bacillus anthracis exposure when administered with the recommended antibacterial drugs. Healthy adult participants (n = 3689) aged 18 to 65 were randomized to receive CYFENDUS vaccination (intramuscularly at 0, 2 weeks) or BioThrax® (Anthrax Vaccine Absorbed) [subcutaneously at 0, 2, 4 weeks]. Immunogenicity at Day 64 (seven weeks after the last CYFENDUS vaccine dose; five weeks after the last BioThrax vaccine dose) was evaluated using a 50 % neutralizing factor (NF50) threshold of protective immunogenicity generated by a toxin neutralizing antibody (TNA) assay, and by evaluating non-inferiority of CYFENDUS to BioThrax vaccination. Safety was assessed by physical exams, vital signs, solicited local injection site and systemic reactogenicity, and unsolicited adverse events (AEs). The prospectively defined success criteria were met for the primary immunogenicity endpoints. The lower bound of the two-sided 95 % confidence interval (CI) for the proportion of CYFENDUS participants with TNA NF50 ≥ 0.56 was above the pre-defined criterion of ≥40 % (95 % CI: 64.5 %, 68.1 %). The lower bound of the two-sided 95 % CI of the difference in the proportion of participants with TNA NF50 ≥ 0.29 in the CYFENDUS versus the BioThrax vaccine group was greater than the pre-defined non-inferiority criterion of −15 % as well as demonstrating statistical superiority (95 % CI: 20.0, 29.2 %), a closed hypothesis test supported by regulatory agencies in well-controlled clinical trials. The most common adverse events (AE) were injection site-related; most reported solicited reactogenicities and AEs were either Grade 1 or 2 severity. The study met the pre-defined endpoint criteria, demonstrating protective level of immune response and non-inferiority of CYFENDUS to BioThrax vaccination. The CYFENDUS vaccine was well-tolerated in healthy adults. Trial Registration:ClinicalTrials.gov Identifier: NCT03877926 •CYFENDUS has comparable safety profile to Anthrax Vaccine Absorbed (BioThrax) in healthy adults•CYFENDUS achieved protective antibody levels up to seven weeks after second vaccination•CYFENDUS-elicited immune response was non-inferior to that of BioThrax•Equivalent immunogenicity was observed across three consecutively manufactured CYFENDUS vaccine lots

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Adjuvants / Adjuvants, Immunologic - administration & dosage / Adjuvants, Vaccine - administration & dosage / Adolescent / Adult / Adults / Adverse events / Aged / Allergy and Immunology / Anthrax / Anthrax - immunology / Anthrax - prevention & control / Anthrax vaccine adsorbed Adjuvanted / anthrax vaccines / Anthrax Vaccines - administration & dosage / Anthrax Vaccines - adverse effects / Anthrax Vaccines - immunology / antibodies / Antibodies, Bacterial - blood / Antibodies, Bacterial - immunology / Antibodies, Neutralizing - blood / Antibodies, Neutralizing - immunology / AV7909 / Bacillus anthracis / Bacillus anthracis - immunology / BioThrax® (Anthrax vaccine adsorbed) / Clinical trials / confidence interval / CPG 7909 / Criteria / CYFENDUS / Disease prevention / Double-Blind Method / Drug dosages / Exposure / Female / Healthy Volunteers / Humans / Immune response / Immune system / Immunogenicity / Immunogenicity, Vaccine / Immunosuppressive agents / injection site / Lower bounds / Male / Middle Aged / Neutralizing / Post-exposure prophylaxis / Post-Exposure Prophylaxis - methods / Safety / Statistical analysis / Toxins / Vaccination / Vaccine / Vaccines / Young Adult