Immunogenicity, safety, and cross-reactivity of an inactivated, adjuvanted, prototype pandemic influenza (H5N1) vaccine: a phase II, double-blind, randomized trial.
BACKGROUND
Avian influenza A virus H5N1 has the potential to cause a pandemic. Adjuvants and whole-virion vaccines are regarded as antigen sparing for pandemic vaccines.


METHODS
A double-blind, randomized trial was performed from 28 August to 22 December 2007 in 402 adults; 301 adults were randomly assigned to receive 2 doses of an inactivated, aluminum-adjuvanted, whole-virion H5N1 vaccine containing 5, 10, or 15 microg of hemagglutinin per dose 28 days apart, and 101 of them received 2 doses of 10 microg of vaccine 14 days apart. The vaccine was manufactured from the recombinant A/Vietman/1194/2004 (NIBRG14) strain. Blood samples were collected for hemagglutination inhibition and microneutralization assays.


RESULTS
All formulations were well tolerated, with no serious adverse events. Most local and systemic reactions were mild or moderate. Immune responses were induced after 1 dose in all vaccination groups. The highest immune response was seen after 2 doses of 15 microg of vaccine, with 90% and 100% seroconversion rates and 90% and 100% of participants having a titer of > or = 1:40 for hemagglutination inhibition and microneutralization assays, respectively. Both the 10- and 15-microg doses met or exceeded European Union licensure criteria. Generally, higher immune responses were elicited in participants vaccinated 28 days apart than those vaccinated 14 days apart. Cross-reaction assays showed that after 2 doses of 10 microg of vaccine, 98% and 87% of participants had a microneutralization titer of > or = 1:40 against heterologous Indonesia and Anhui strains, respectively.


CONCLUSIONS
The inactivated, aluminum-adjuvanted, whole-virion H5N1 vaccine not only showed good immunogenicity and safety but also elicited significant cross-reactivity against heterologous H5N1 strains in clade 2.


BACKGROUND
ClinicalTrials.gov identifier: NCT00535665.
Wu
Jiang
J
Beijing Centers for Diseases Control and Prevention, Beijing, China.
Fang
Han-Hua
HH
Chen
Jiang-Ting
JT
Zhou
Ji-Chen
JC
Feng
Zi-Jian
ZJ
Li
Chang-Gui
CG
Qiu
Yuan-Zheng
YZ
Liu
Yan
Y
Lu
Min
M
Liu
Li-Ying
LY
Dong
Shan-Shan
SS
Gao
Qiang
Q
Zhang
Xiao-Mei
XM
Wang
Nan
N
Yin
Wei-Dong
WD
Dong
Xiao-Ping
XP
D000276:Adjuvants, Immunologic / Q000009:adverse effects; D000293:Adolescent; D000328:Adult; D000536:Aluminum Hydroxide / Q000009:adverse effects / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood*; D003429:Cross Reactions; D004196:Disease Outbreaks / Q000517:prevention & control; D004311:Double-Blind Method; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated; D000536:Aluminum Hydroxide