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J Microbiol Immunol Infect · Dec 2013
Randomized Controlled TrialThe Madin-Darby canine kidney cell culture derived influenza A/H5N1 vaccine: a phase I trial in Taiwan.
- Sung-Ching Pan, Hsiang-Chi Kung, Tsui-Mai Kao, Hsio Wu, Shao-Xing Dong, Mei-Hua Hu, Ai-Hsiang Chou, Pele Chong, Szu-Min Hsieh, and Shan-Chwen Chang.
- Department of Internal Medicine, National Taiwan University Hospital, Taiwan; College of Medicine, National Taiwan University, Taipei, Taiwan.
- J Microbiol Immunol Infect. 2013 Dec 1; 46 (6): 448-55.
BackgroundAvian H5N1 influenza has caused human infections globally and has a high mortality rate. Rapid production of effective vaccines is needed.MethodsA 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 3 μg hemagglutinin (HA), 3 μg HA with 300 μg aluminum phosphate (AlPO4), 6 μg HA, and 6 μg HA with 300 μg 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.ResultsSixty healthy individuals were enrolled. The neutralization assay showed a significant immune response in the 6 μg 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 6 μg 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 3 μg and 6 μg 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.ConclusionMDCK 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.Copyright © 2012. Published by Elsevier B.V.
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