The safety and immunogenicity of a cell-derived adjuvanted H5N1 vaccine – A phase I randomized clinical trial
Journal
Journal of Microbiology, Immunology and Infection
Journal Volume
52
Journal Issue
5
Pages
685-692
Date Issued
2019
Author(s)
Li Y.-H.
Hsieh E.-F.
Lee H.-C.
Lin T.-W.
Lai K.-L.
Chen C.
Shi-Chung Chang S.
Abstract
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.). ? 2019
SDGs
Other Subjects
aluminum potassium sulfate; influenza vaccine; Influenza virus hemagglutinin; neutralizing antibody; aluminum derivative; hemagglutinin, avian influenza A virus; immunological adjuvant; inactivated vaccine; influenza vaccine; neutralizing antibody; virus antibody; adult; animal cell; antibody response; antibody titer; arthralgia; Article; controlled study; coughing; dermatitis; drug safety; drug tolerability; dysmenorrhea; erythrocyte; fatigue; female; headache; hemagglutination inhibition; horse; human; human experiment; Influenza A virus (H5N1); injection site bleeding; injection site erythema; injection site pain; injection site pruritus; injection site reaction; injection site swelling; male; MDCK cell line; middle aged; myalgia; nonhuman; open study; phase 1 clinical trial; prospective study; randomized controlled trial; rigor; seroconversion; single blind procedure; turkey (bird); vaccine immunogenicity; young adult; adverse drug reaction; adverse event; animal; avian influenza; bird; blood; clinical trial; dog; hemagglutination inhibition test; immunology; influenza; intramuscular drug administration; pandemic; pathophysiology; safety; Taiwan; vaccination; Adjuvants, Immunologic; Adult; Aluminum Compounds; Animals; Antibodies, Neutralizing; Antibodies, Viral; Birds; Dogs; Drug-Related Side Effects and Adverse Reactions; Female; Hemagglutination Inhibition Tests; Hemagglutinin Glycoproteins, Influenza Virus; Horses; Humans; Immunogenicity, Vaccine; Influenza A Virus, H5N1 Subtype; Influenza in Birds; Influenza Vaccines; Influenza, Human; Injections, Intramuscular; Madin Darby Canine Kidney Cells; Male; Middle Aged; Pandemics; Safety; Seroconversion; Taiwan; Vaccination; Vaccines, Inactivated; Young Adult
Publisher
Elsevier Ltd
Type
journal article