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Volume 46, Number 6, December 2013

The 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, Shan-Chwen Chang


Received: June 21, 2012    Revised: July 20, 2012    Accepted: July 30, 2012   

 

Corresponding author:

Szu-Min Hsieh, Department of Internal Medicine, National Taiwan University Hospital, Taiwan
College of Medicine, National Taiwan University, Taipei, Taiwan
Corresponding Author InformationCorresponding author. Department of Internal Medicine, National Taiwan University Hospital, #7 Chung-Shan South Road, Taipei 100, Taiwan.



 

Background and purpose: 

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.



 

Key words:

AdjuvantCell cultureInfluenza A/H5N1 vaccines