The safety and immunogenicity of a cell-derived adjuvanted H5N1 vaccine – A phase I randomized clinical trial

• Published in: Journal of Microbiology, Immunology and Infection
• Main Authors: Aristine Cheng, Szu-Min Hsieh, Sung-Ching Pan, Yu-Han Li, Erh-Fang Hsieh, Hsiang-Chi Lee, Ting-Wan Lin, Kuan-Lang Lai, Charles Chen, Stanley Shi-Chung Chang, Shan-Chwen Chang
• Format: Article in Journal/Newspaper
• Language: English
• Published: Elsevier 2019
• Subjects: Microbiology; QR1-502; Darby; Avian flu
• Online Access: https://doi.org/10.1016/j.jmii.2019.03.009; https://doaj.org/article/b0907daaec2e4aae84ad5f05d69fb80a

Background: Development of an efficacious egg-free mock-up H5N1 vaccine is key to our preparedness against pandemic avian flu. Methods: This is a single-center, randomized, observer-blinded phase I clinical trial evaluating the safety and immunogenicity of an alum-adjuvanted Madin–Darby canine kidney (MDCK)-derived inactivated whole-virion H5N1 influenza vaccine in healthy adults. Hemagglutination inhibition (HAI) and neutralizing antibody titers were measured using horse and turkey red blood cells (RBCs). Results: Thirty-six adult subjects were randomized to receive two doses of 0.5 mL of the MDCK-derived H5N1 alum-adjuvanted vaccine containing 7.5, 15, or 30 μg of hemagglutinin (HA) 21 days apart. The candidate vaccine was well tolerated and safe across the three dosing groups. The most frequent adverse event was injection site pain (46.5%). Both HAI and neutralizing antibody titers increased after each vaccination in all three dosing groups. The best HAI responses, namely a seroconversion rate of 91.7% and a geometric mean ratio of 9.51 were achieved with the HA dose of 30 μg assayed using horse RBCs at day 42. HAI titers against H5N1 avian influenza virus was significantly higher when measured using horse RBCs compared with turkey RBCs. Conclusions: This Phase I trial showed the MDCK-derived H5N1 candidate vaccine is safe and immunogenic. The source of RBCs has a significant impact on the measurement of HAI titers (ClinicalTrials.gov number: NCT01675284.). Keywords: Influenza A, Avian influenza, H5N1, Vaccination, Immune response