An adjuvanted, low-dose, pandemic influenza A (H5N1) vaccine candidate is safe, immunogenic, and induces cross-reactive immune responses in healthy adults.
BACKGROUND
To protect a naive global population against pandemic influenza, pandemic vaccines should be effective at low antigen doses, because of limited manufacturing capacity.


METHODS
In a multicenter, randomized, blind-observer phase 1 trial, groups of 50 healthy young adults received 2 doses, 21 days apart, of influenza A/Vietnam/1194/2004 NIBRG-14 (H5N1) vaccine containing 1.9, 3.8, 7.5 or 15 microg of hemagglutinin with oil-in-water emulsion adjuvant or 7.5 microg of hemagglutinin without adjuvant. Safety was monitored to day 42. Homologous hemagglutination-inhibition (HI) and microneutralization titers were determined after each vaccination. Cross-reactivity against A/Indonesia/05/2005 RG2 was tested after the second vaccination.


RESULTS
No vaccine-related significant or serious adverse events occurred. Injection site reactions, but not systemic reactions, were more frequent with adjuvant than without. Even with only 1.9 microg of hemagglutinin plus adjuvant, 72% of subjects had HI titers >or=1:32 after 2 doses. This proportion was 81%-89% with higher adjuvanted doses but was only 34% without adjuvant. Adjuvanted vaccine induced cross-neutralizing antibodies in 39%-65% of samples, versus 7% without adjuvant.


CONCLUSIONS
The emulsion-adjuvanted pandemic influenza vaccine candidate was safe, immunogenic, and induced cross-reactive antibodies. This adjuvanted 1.9-microg candidate is the lowest effective dose tested to date. This could have a major impact on prepandemic vaccination strategies with stockpiled batches of vaccine.


BACKGROUND
ClinicalTrials.gov identifier: NCT00457509 .
Levie
Karin
K
Ecole de Santé Publique, Université Catholique de Louvain, Brussels. karin.levie@centredesante.ucl.ac.be
Leroux-Roels
Isabel
I
Hoppenbrouwers
Karel
K
Kervyn
Anne-Diane
AD
Vandermeulen
Corinne
C
Forgus
Sheron
S
Leroux-Roels
Geert
G
Pichon
Sylvie
S
Kusters
Inca
I
D000276:Adjuvants, Immunologic; D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D003429:Cross Reactions; D004306:Dose-Response Relationship, Immunologic; D005260:Female; 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*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D016037:Single-Blind Method
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007252:Influenza Vaccines