title: The Madin-Darby canine kidney cell culture derived influenza A/H5N1 vaccine: a phase I trial in Taiwan.
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 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.
  
  
  RESULTS
  Sixty 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taiwan; College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Sung-Ching
authors.initials: SC
authors.lastname: Pan
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taiwan.
authors.forename: Hsiang-Chi
authors.initials: HC
authors.lastname: Kung
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taiwan.
authors.forename: Tsui-Mai
authors.initials: TM
authors.lastname: Kao
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taiwan.
authors.forename: Hsio
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taiwan.
authors.forename: Shao-Xing
authors.initials: SX
authors.lastname: Dong
authors.affiliation: Vaccine R&D Center, National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan.
authors.forename: Mei-Hua
authors.initials: MH
authors.lastname: Hu
authors.affiliation: Vaccine R&D Center, National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan.
authors.forename: Ai-Hsiang
authors.initials: AH
authors.lastname: Chou
authors.affiliation: Vaccine R&D Center, National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan; Graduate Institute of Immunology, China Medical University, Taichung, Taiwan.
authors.forename: Pele
authors.initials: P
authors.lastname: Chong
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taiwan; College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: hsmaids@hotmail.com.
authors.forename: Szu-Min
authors.initials: SM
authors.lastname: Hsieh
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taiwan; College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Shan-Chwen
authors.initials: SC
authors.lastname: Chang
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000328:Adult; D017607:Aluminum Compounds / Q000008:administration & dosage; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D004285:Dogs; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D064368:Healthy Volunteers; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology* / Q000302:isolation & purification; D007251:Influenza, Human / Q000517:prevention & control*; D007273:Injections, Intramuscular; D061985:Madin Darby Canine Kidney Cells; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D010710:Phosphates / Q000008:administration & dosage; D011446:Prospective Studies; D016037:Single-Blind Method; D013624:Taiwan; D014611:Vaccination / Q000379:methods; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000302:isolation & purification; D014776:Virus Cultivation / Q000379:methods; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D017607:Aluminum Compounds; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007252:Influenza Vaccines; D010710:Phosphates; D015164:Vaccines, Inactivated; C012714:aluminum phosphate