The Madin-Darby canine kidney cell culture derived influenza A/H5N1 vaccine: A Phase I trial in Taiwan
Journal
Journal of Microbiology, Immunology and Infection
Journal Volume
46
Journal Issue
6
Pages
448-455
Date Issued
2013
Author(s)
Kao T.-M.
Wu H.
Dong S.-X.
Hu M.-H.
Chou A.-H.
Chong P.
Abstract
Background: Avian H5N1 influenza has caused human infections globally and has a high mortality rate. Rapid production of effective vaccines is needed. Methods: A phase 1, randomized, observer-blinded clinical trial was conducted to examine the safety and immunogenicity of an inactivated whole virion vaccine against the influenza A/H5N1 virus produced from the Madin-Darby canine kidney (MDCK) cell line. Participants were randomized to four groups and administered two intramuscular doses of vaccine containing 3μg hemagglutinin (HA), 3μg HA with 300μg aluminum phosphate (AlPO4), 6μg HA, and 6μg HA with 300μg AlPO4, respectively, at two visits, 21 days apart. Serum hemagglutination inhibition (HAI) and neutralizing antibody levels were determined at baseline and on Days 21 and 42. Results: Sixty healthy individuals were enrolled. The neutralization assay showed a significant immune response in the 6μg with ALPO4 group on Day 42 compared to pre-vaccination levels (11.32±9.77 vs. 4.00±0, p=0.02). The adjuvant effect in neutralization assay was also significant on Day 42 in the 6μg group (4.52±1.94 without adjuvant vs. 11.32±9.77 with adjuvant, p=0.02). HAI assay also showed an aluminum adjuvant-induced increasing trend in HAI geometric mean titer on Day 42 in the 3μg and 6μg groups (6.02 versus 8.20, p=0.05 and 5.74 versus 8.21, p=0.14). The most frequent adverse event was local pain (20% to 60%). There were no vaccine-related severe adverse effects. Conclusion: MDCK cell line-derived H5N1 vaccine was well tolerated. It is necessary to investigate further the immunogenicity of higher antigen doses and the role of aluminum adjuvant in augmenting the effect of the vaccine. ? 2012 .
SDGs
Other Subjects
alanine aminotransferase; aluminum phosphate; aspartate aminotransferase; bilirubin; influenza vaccine; Influenza virus hemagglutinin; neutralizing antibody; adult; animal cell; antibody blood level; antibody titer; arthralgia; article; controlled study; dizziness; double blind procedure; drug safety; drug tolerability; fatigue; female; fever; headache; hemagglutination inhibition; hematoma; human; humoral immunity; hyperbilirubinemia; immune response; immunogenicity; influenza A (H5N1); influenza vaccination; Influenza virus A H5N1; injection site pain; injection site reaction; injection site swelling; liver function test; male; MDCK cell; myalgia; nonhuman; normal human; phase 1 clinical trial; prospective study; randomized controlled trial; seroconversion; shivering; side effect; single drug dose; skin redness; Taiwan; upper respiratory tract infection; virus neutralization; Adjuvant; Cell culture; Influenza A/H5N1 vaccines; Adjuvants, Immunologic; Adult; Aluminum Compounds; Animals; Antibodies, Neutralizing; Antibodies, Viral; Dogs; Drug-Related Side Effects and Adverse Reactions; Female; Healthy Volunteers; Hemagglutination Inhibition Tests; Humans; Influenza A Virus, H5N1 Subtype; Influenza Vaccines; Influenza, Human; Injections, Intramuscular; Madin Darby Canine Kidney Cells; Male; Middle Aged; Neutralization Tests; Phosphates; Prospective Studies; Single-Blind Method; Taiwan; Vaccination; Vaccines, Inactivated; Virus Cultivation; Young Adult
Type
journal article